Drug ID	DRG00141
Drug Name	Beta-carboline derivative
Synonyms	66863-43-2; Boc-L-1,2,3,4-Tetrahydronorharman-3-carboxylic acid; Boc-L-Tpi-OH; (S)-2-(tert-butoxycarbonyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid; (S)-2-Boc-1,2,3,4-tetrahydronorharmane-3-carboxylic acid; Boc-L-1,2,3,4-tetrahydro-norharman-3-carboxylic acid; (3S)-2-[(2-methylpropan-2-yl)oxycarbonyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylic acid; MFCD00800580; FHEPEWKHTOVVAT-AWEZNQCLSA-N; SCHEMBL5880416; CHEMBL2032051; AKOS015948717; N-alpha-tert-Butyloxycarbonyl-1,2,3,4-tetrahydronorharman-L-3-carboxylic acid; AC-5891; CS-W012030; (3S)-2-(tert-butoxycarbonyl)-1H,3H,4H,9H-pyrido[3,4-b]indole-3-carboxylic acid; PS-12017; FT-0659177; A50152; EN300-1071066; N-; A-Boc-L-1,2,3,4-tetrahydronorharmane-3-carboxylic acid; Boc-L-1,2,3,4-tetrahydronorharman-3-carboxylic acid, AldrichCPR; (3S)-2-[(tert-butoxy)carbonyl]-1H,2H,3H,4H,9H-pyrido[3,4-b]indole-3-carboxylic acid; (S)-2-(tert-butoxycarbonyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylicacid; Boc-Tpi-OH;Boc-L-1,2,3,4-Tetrahydro--carboline-3-carboxylic acid;Boc-L-tryptoline-3-carboxylic acid;Boc-L-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylic acid    Click to Show/Hide
Structure
	3D MOL			2D MOL
Formula	C17H20N2O4
#Ro5 Violations (Lipinski): 0	Molecular Weight (mw)			316.35
	Lipid-water partition coefficient (xlogp)			2.4
	Hydrogen Bond Donor Count (hbonddonor)			2
	Hydrogen Bond Acceptor Count (hbondacc)			4
	Rotatable Bond Count (rotbonds)			3
PubChem CID	1268155
Canonical smiles	CC(C)(C)OC(=O)N1CC2=C(CC1C(=O)O)C3=CC=CC=C3N2
InChI	InChI=1S/C17H20N2O4/c1-17(2,3)23-16(22)19-9-13-11(8-14(19)15(20)21)10-6-4-5-7-12(10)18-13/h4-7,14,18H,8-9H2,1-3H3,(H,20,21)/t14-/m0/s1
InChIKey	FHEPEWKHTOVVAT-AWEZNQCLSA-N
IUPAC Name	(3S)-2-[(2-methylpropan-2-yl)oxycarbonyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-3-carboxylic acid

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	7.46 ± 8.95%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	8.23 ± 12.04%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	13.42 ± 8.68%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	17.97 ± 14.64%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	18.86 ± 19.46%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	20.65 ± 18.94%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	22.13 ± 14.89%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	23.45 ± 15.31%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 9 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	25.45 ± 15.37%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 10 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	25.46 ± 12.12%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 11 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	29.22 ± 10.26%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 12 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	32.73 ± 18.69%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 13 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	34.55 ± 38.43%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 14 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	35.41 ± 13.56%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 15 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	37.65 ± 28.53%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 16 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	44.67 ± 41.08%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 17 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	48.25 ± 45.02%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 18 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	59.37 ± 37.02%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 19 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.29 ± 0.35 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 20 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.65 ± 0.51 mg
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 21 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.01 ± 0.48 mg
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 22 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	38.70%
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 23 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	49.60%
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 24 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	60.70%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	9.06 ± 15.43%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	11.55 ± 9.28%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	14.38 ± 20.13%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	15.43 ± 10.94%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	18.99 ± 8.96%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	21.39 ± 15.60%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	23.08 ± 13.89%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	23.58 ± 11.46%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 9 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	25.69 ± 11.36%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 10 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	26.54 ± 10.33%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.05mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 11 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	29.04 ± 22.58%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 12 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	32.32 ± 19.55%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 13 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	34.48 ± 21.03%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 14 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	38.33 ± 11.25%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.10mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 15 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	41.28 ± 13.33%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 16 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	44.27 ± 42.46%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 17 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	52.22 ± 33.12%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 18 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	54.39 ± 23.67%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 19 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.47 ± 0.27 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 20 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.79 ± 0.54 mg
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 21 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.35 ± 0.43 mg
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 22 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	28.30%
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 23 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	45.40%
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 24 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	55.20%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	10.36 ± 22.24%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	14.36 ± 28.12%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	22.37 ± 34.30%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	40.78 ± 32.03%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	46.45 ± 5.46%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	49.09 ± 29.03%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.05 ± 0.76 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	37.50%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	12.25 ± 26.18%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	12.32 ± 14.94%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	17.23 ± 13.55%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	18.24 ± 11.56%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	29.25 ± 17.12%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	39.23 ± 17.12%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.35 ± 0.55 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	28.40%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	13.29 ± 12.47%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	22.23 ± 14.66%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	24.33 ± 6.49%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	32.19 ± 14.78%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	37.25 ± 21.12%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	39.38 ± 13.48%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.39 ± 0.28 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	57.60%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	13.54 ± 18.46%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	18.77 ± 13.45%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	22.17 ± 28.57%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	28.12 ± 19.81%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	34.55 ± 13.29%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	40.67 ± 33.57%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.97 ± 0.53 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	40%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	14.23 ± 12.18%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	16.69 ± 10.33%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	28.55 ± 12.36%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	35.05 ± 29.27%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	35.19 ± 21.33%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	36.45 ± 27.36%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.59 ± 0.44 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	51.50%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	15.25 ± 22.46%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	16.13 ± 13.39%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	27.32 ± 14.88%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	33.01 ± 38.16%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	38.01 ± 29.23%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	41.23 ± 44.46%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.43 ± 0.38 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	56.40%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	15.32 ± 11.18%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	21.12 ± 14.45%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	31.34 ± 31.32%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	37.20 ± 15.13%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	40.56 ± 8.32%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	45.46 ± 23.54%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.70 ± 0.41 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	48.20%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	15.68 ± 11.32%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	18.79 ± 15.74%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	21.35 ± 27.20%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	23.17 ± 25.32%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	25.05 ± 18.13%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	49.74 ± 35.11%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.73 ± 0.31 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	47.30%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	16.03 ± 8.96%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	25.88 ± 11.77%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	35.79 ± 9.32%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	39.47 ± 25.44%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	45.77 ± 26.32%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	47.36 ± 28.21%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.85 ± 0.54 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	43.60%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	18.32 ± 37.12%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	22.45 ± 43.22%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	32.33 ± 22.89%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	41.83 ± 39.35%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	47.33 ± 19.47%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	51.25 ± 11.84%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.89 ± 0.60 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	42.40%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	19.22 ± 17.46%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	28.79 ± 10.13%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	37.58 ± 20.23%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	42.03 ± 6.41%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	46.48 ± 9.15%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	48.23 ± 14.23%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.55 ± 0.43 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.81 ± 0.38 mg
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 9 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.21 ± 0.47 mg
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 10 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	32.60%
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 11 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	44.80%
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 12 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	52.70%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	19.25 ± 14.39%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	23.19 ± 15.36%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	30.75 ± 24.24%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	38.20 ± 32.09%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	40.36 ± 23.49%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	42.43 ± 27.22%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.62 ± 0.43 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	50.60%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	19.45 ± 21.79%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	21.24 ± 15.74%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	22.12 ± 26.22%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	34.56 ± 35.77%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	39.25 ± 17.48%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	45.23 ± 11.14%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.45 ± 0.42 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	55.80%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	20.94 ± 14.46%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	28.87 ± 21.93%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	30.25 ± 31.49%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	35.75 ± 30.35%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	41.18 ± 17.45%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	43.23 ± 32.49%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.61 ± 0.32 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.20 ± 0.43 mg
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 9 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.75 ± 0.66 mg
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 10 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	16.20%
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 11 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	32.90%
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 12 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	50.90%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	21.55 ± 17.29%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	29.38 ± 16.45%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	35.13 ± 22.25%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	37.12 ± 15.25%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	38.16 ± 19.26%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	46.08 ± 19.94%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.41 ± 0.49 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.41 ± 0.58 mg
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 9 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	2.91 ± 0.67 mg
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 10 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	11.30%
Administration Time	30 min
Administration Dosage	0.05 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 11 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	26.50%
Administration Time	30 min
Administration Dosage	0.1 mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 12 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	57%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Experiment 1 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	25.07 ± 11.21%
Evaluation Method	Tail flick method
Administration Time	180min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 2 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	26.47 ± 27.55%
Evaluation Method	Tail flick method
Administration Time	150min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 3 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	30.56 ± 21.46%
Evaluation Method	Tail flick method
Administration Time	30min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 4 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	38.45 ± 19.66%
Evaluation Method	Tail flick method
Administration Time	120min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 5 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	42.32 ± 16.41%
Evaluation Method	Tail flick method
Administration Time	60min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 6 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Pain threshold variation	44.13 ± 28.22%
Evaluation Method	Tail flick method
Administration Time	90min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were prescreened for analgesic activity at a dose of 0.15 mmol/kg. For each animal, pain thresholds were estimated at 30, 60, 120, 150 and 180 min following vehicle or drug administration. -Carboline-tripeptide conjugates exhibited moderate to good analgesic activity, with compounds 4a,e,k,l,o,p demonstrating especially good analgesic properties. All pain thresholds were increased after 30 min, yet maximal pain thresholds occurred at different time points for various synthetic derivatives. For example, the maximal pain thresholds for 4a,c,e,h,m were observed after 60 min, whereas for 4d,g,k,l,n,o,p this value was 90 min, and for 4b,f,i,q,r, 120 min post drug administration. The duration of the analgesic action of 4a,b,c,d,e,f,i,j was 150 min, while the same value for 4k,l,m,n,o,p was 180 min. We speculate that the physiological difference in analgesic activity is closely related to the tripeptide sequences of the -carbolines.    Click to Show/Hide
In Vivo Model	Male ICR mice.
Experiment 7 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema weight	1.78 ± 0.35 mg
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.
Experiment 8 Reporting the Activity Data of This PDC					[1]
Indication	Mesenteric ischemia and reperfusion injury
Efficacy Data	Edema inhibition rate	45.70%
Administration Time	30 min
Administration Dosage	0.15mmol/kg
MOA of PDC	It has been reported that some short peptides with certain sequences may be used as analgesic agents. In addition, our recent research findings indicated that some tripeptides with AA-Phe-Trp sequence present good analgesic activities. Since reactive oxygen species (ROS) and inflammatory leukocytes play an important role in the pathogenesis of I/R injury, antioxidant therapy and inhibition of post-ischemic neutrophil infiltration may have therapeutic efficacy during I/R injury. Ideally, I/R injury can be treated by a combination of the therapeutic agents. Generally, when two synergistic agents are administered individually but simultaneously, they will be transported to the site of action with different efficiencies. However, there are potential advantages in giving the co-administered agents as a single chemical entity. It is desirable to have the two synergistic agents reach a site simultaneously. Considering the antioxidant properties of β-carboline alkaloids coupled with the analgesic activity observed with AA-Phe-Trp tripeptides, we hypothesized that β-carboline and tripeptide (AA-Phe-Trp) conjugates might exhibit both enhanced antioxidant and analgesic activities. To test this hypothesis, we have synthesized a series of novel β-carboline-tripeptide (AA-Phe-Trp) conjugates, and evaluated their biological capacity to protect against mesenteric I/R injury.    Click to Show/Hide
Description	All compounds were evaluated for anti-inflammatory capacity in a xylene-induced ear edema model. Briefly, this in vivo assay involves oral administration of test compounds in 0.5% carboxymethyl cellulose (CMC) suspension. Each compound was initially tested at 0.15 mmol/kg, and all revealed significant protection against xylene-induced inflammation, suggesting potent anti-inflammatory capacity. Since compounds (4a,e,k,o,p) exhibit good analgesic activities in the tail flick assay and superior anti-inflammatory activities in the xylene-induced ear edema model, these compounds were then examined in the same assay at lower doses to establish the detailed pharmacological activity profile. From Table 4, we noticed a dose-dependent anti-inflammatory response for 4a,e,k,o,p.    Click to Show/Hide
In Vivo Model	Male ICR mice xylene-induced ear edema model.

Ref 1	Novel -carboline-tripeptide conjugates attenuate mesenteric ischemia/reperfusion injury in the rat. Bi W, Bi Y, Xue P, Zhang Y, Gao X, Wang Z, Li M, Baudy-Floc'h M, Ngerebara N, Li X, Gibson KM, Bi L.