Objective: To assess the antiangiogenic activity of fenugreek. Methods: Different fractions of fe... more Objective: To assess the antiangiogenic activity of fenugreek. Methods: Different fractions of fenugreek crude extracts were prepared and their anti-angiogenic properties were assessed using the ex vivo rat aortic ring assay and in vivo chicken embryo chorioallantoic membrane (CAM) assay. They were investigated for their direct cytotoxic activity in the MCF7 cells using the MTT assay. Results: The ethanol extract showed 100% inhibition of blood vessel outgrowth from primary tissue explants in the rat aortic ring assay at a concentration of 100 mg/mL while the other extracts did not show significant antiangiogenic activity. The ethanol extract was therefore investigated at varying concentrations and exhibited a significant dose dependent effect. The CAM assay coincided with the results of the aortic ring assay as ethanol extract showed a significant inhibition of formation of new blood vessels. The extracts only showed anti-proliferative activity at the highest concentration of 400 mg/mL towards MCF7 breast cancer cell lines in the MTT assay. Conclusions: Findings of the both assays confirmed that the ethanol extract inhibited vascularization significantly. Further studies on the ethanol extract would be beneficial in isolating the active ingredient responsible for the inhibition.
1. Eleven selected flavonoids were studied to evaluate their effects on the rat isolated ileum an... more 1. Eleven selected flavonoids were studied to evaluate their effects on the rat isolated ileum and to determine their structure-activity relationships. 2. The flavonoids rutin and 3',5,7-trihydroxy-4' methoxyflavone-7-rutinoside, which have a sugar moiety (O-rha-glu), had no significant effect on the ileum, indicating that the presence of sugar substitution reduces the biological activity of the flavonoids. 3. Nine other flavonoids caused inhibition of tonic and phasic contractions of the ileum with the following order of potency from highest to lowest: galangin, quercetin, chrysin, xanthomicrol, flavone, naringenin, fisetin, morin, and flavanone. 4. Flavones were more potent than flavanones, indicating that the double bond at carbon 2-3 increases the potency of the flavonoid. 5. Galangin, quercetin, chrysin, and xanthomicrol, which have hydroxyl substituents on carbon 3 and/or 5, showed higher potency than flavone, indicating that such hydroxyl groups are essential for the activity. 6. Galangin was more potent than quercetin, morin, and fisetin, suggesting that the hydroxyl substituents on ring B attenuate the potency. 7. Quercetin caused more potent relaxation of the ileum than morin, suggesting that the presence of a hydroxyl group at C-2' of ring B attenuates the myolytic activity.
The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance i... more The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance in coronary arteries.Rings of porcine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by incubating the tissues with nitroglycerin (10−4M) for 90 min, followed by repeated rinsing for 1 h. Control rings that had not been exposed previously to nitroglycerin, but were otherwise treated identically, were studied simultaneously. The rings were contracted with U46619 (1–3 × 10−9M) and concentration–response curves to nitroglycerin (10−9–10−4M) were obtained.Nitrate tolerance was evident by a 15- to 20-fold rightward shift in the concentration–response curve to nitroglycerin in rings with and without endothelium exposed previously to the drug for 90 min. Addition of melatonin (10−9–10−7M) to the organ chamber during the 90-min incubation period with nitroglycerin partially inhibited nitrate tolerance in coronary arteries with intact endothelium; however, melatonin had no effect on nitrate tolerance in coronary arteries without endothelium.The effect of melatonin on nitrate tolerance in coronary arteries with endothelium was abolished by the melatonin receptor antagonist, S20928 (10−6M). In contrast to melatonin, the selective MT3-melatonin receptor agonist, 5-MCA-NAT (10−8–10−7M), had no effect on nitrate tolerance in coronary arteries.The results demonstrate that melatonin, acting via specific melatonin receptors, inhibits nitrate tolerance in coronary arteries and that this effect is dependent on the presence of the vascular endothelium.The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance in coronary arteries.Rings of porcine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by incubating the tissues with nitroglycerin (10−4M) for 90 min, followed by repeated rinsing for 1 h. Control rings that had not been exposed previously to nitroglycerin, but were otherwise treated identically, were studied simultaneously. The rings were contracted with U46619 (1–3 × 10−9M) and concentration–response curves to nitroglycerin (10−9–10−4M) were obtained.Nitrate tolerance was evident by a 15- to 20-fold rightward shift in the concentration–response curve to nitroglycerin in rings with and without endothelium exposed previously to the drug for 90 min. Addition of melatonin (10−9–10−7M) to the organ chamber during the 90-min incubation period with nitroglycerin partially inhibited nitrate tolerance in coronary arteries with intact endothelium; however, melatonin had no effect on nitrate tolerance in coronary arteries without endothelium.The effect of melatonin on nitrate tolerance in coronary arteries with endothelium was abolished by the melatonin receptor antagonist, S20928 (10−6M). In contrast to melatonin, the selective MT3-melatonin receptor agonist, 5-MCA-NAT (10−8–10−7M), had no effect on nitrate tolerance in coronary arteries.The results demonstrate that melatonin, acting via specific melatonin receptors, inhibits nitrate tolerance in coronary arteries and that this effect is dependent on the presence of the vascular endothelium.British Journal of Pharmacology (2003) 139, 1326–1332. doi:10.1038/sj.bjp.0705383
Objective: To assess the antiangiogenic activity of fenugreek. Methods: Different fractions of fe... more Objective: To assess the antiangiogenic activity of fenugreek. Methods: Different fractions of fenugreek crude extracts were prepared and their anti-angiogenic properties were assessed using the ex vivo rat aortic ring assay and in vivo chicken embryo chorioallantoic membrane (CAM) assay. They were investigated for their direct cytotoxic activity in the MCF7 cells using the MTT assay. Results: The ethanol extract showed 100% inhibition of blood vessel outgrowth from primary tissue explants in the rat aortic ring assay at a concentration of 100 mg/mL while the other extracts did not show significant antiangiogenic activity. The ethanol extract was therefore investigated at varying concentrations and exhibited a significant dose dependent effect. The CAM assay coincided with the results of the aortic ring assay as ethanol extract showed a significant inhibition of formation of new blood vessels. The extracts only showed anti-proliferative activity at the highest concentration of 400 mg/mL towards MCF7 breast cancer cell lines in the MTT assay. Conclusions: Findings of the both assays confirmed that the ethanol extract inhibited vascularization significantly. Further studies on the ethanol extract would be beneficial in isolating the active ingredient responsible for the inhibition.
1. Eleven selected flavonoids were studied to evaluate their effects on the rat isolated ileum an... more 1. Eleven selected flavonoids were studied to evaluate their effects on the rat isolated ileum and to determine their structure-activity relationships. 2. The flavonoids rutin and 3',5,7-trihydroxy-4' methoxyflavone-7-rutinoside, which have a sugar moiety (O-rha-glu), had no significant effect on the ileum, indicating that the presence of sugar substitution reduces the biological activity of the flavonoids. 3. Nine other flavonoids caused inhibition of tonic and phasic contractions of the ileum with the following order of potency from highest to lowest: galangin, quercetin, chrysin, xanthomicrol, flavone, naringenin, fisetin, morin, and flavanone. 4. Flavones were more potent than flavanones, indicating that the double bond at carbon 2-3 increases the potency of the flavonoid. 5. Galangin, quercetin, chrysin, and xanthomicrol, which have hydroxyl substituents on carbon 3 and/or 5, showed higher potency than flavone, indicating that such hydroxyl groups are essential for the activity. 6. Galangin was more potent than quercetin, morin, and fisetin, suggesting that the hydroxyl substituents on ring B attenuate the potency. 7. Quercetin caused more potent relaxation of the ileum than morin, suggesting that the presence of a hydroxyl group at C-2' of ring B attenuates the myolytic activity.
The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance i... more The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance in coronary arteries.Rings of porcine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by incubating the tissues with nitroglycerin (10−4M) for 90 min, followed by repeated rinsing for 1 h. Control rings that had not been exposed previously to nitroglycerin, but were otherwise treated identically, were studied simultaneously. The rings were contracted with U46619 (1–3 × 10−9M) and concentration–response curves to nitroglycerin (10−9–10−4M) were obtained.Nitrate tolerance was evident by a 15- to 20-fold rightward shift in the concentration–response curve to nitroglycerin in rings with and without endothelium exposed previously to the drug for 90 min. Addition of melatonin (10−9–10−7M) to the organ chamber during the 90-min incubation period with nitroglycerin partially inhibited nitrate tolerance in coronary arteries with intact endothelium; however, melatonin had no effect on nitrate tolerance in coronary arteries without endothelium.The effect of melatonin on nitrate tolerance in coronary arteries with endothelium was abolished by the melatonin receptor antagonist, S20928 (10−6M). In contrast to melatonin, the selective MT3-melatonin receptor agonist, 5-MCA-NAT (10−8–10−7M), had no effect on nitrate tolerance in coronary arteries.The results demonstrate that melatonin, acting via specific melatonin receptors, inhibits nitrate tolerance in coronary arteries and that this effect is dependent on the presence of the vascular endothelium.The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance in coronary arteries.Rings of porcine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by incubating the tissues with nitroglycerin (10−4M) for 90 min, followed by repeated rinsing for 1 h. Control rings that had not been exposed previously to nitroglycerin, but were otherwise treated identically, were studied simultaneously. The rings were contracted with U46619 (1–3 × 10−9M) and concentration–response curves to nitroglycerin (10−9–10−4M) were obtained.Nitrate tolerance was evident by a 15- to 20-fold rightward shift in the concentration–response curve to nitroglycerin in rings with and without endothelium exposed previously to the drug for 90 min. Addition of melatonin (10−9–10−7M) to the organ chamber during the 90-min incubation period with nitroglycerin partially inhibited nitrate tolerance in coronary arteries with intact endothelium; however, melatonin had no effect on nitrate tolerance in coronary arteries without endothelium.The effect of melatonin on nitrate tolerance in coronary arteries with endothelium was abolished by the melatonin receptor antagonist, S20928 (10−6M). In contrast to melatonin, the selective MT3-melatonin receptor agonist, 5-MCA-NAT (10−8–10−7M), had no effect on nitrate tolerance in coronary arteries.The results demonstrate that melatonin, acting via specific melatonin receptors, inhibits nitrate tolerance in coronary arteries and that this effect is dependent on the presence of the vascular endothelium.British Journal of Pharmacology (2003) 139, 1326–1332. doi:10.1038/sj.bjp.0705383
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