Vasodilatory Effects and Mechanisms of Action of Bacopa monnieri Active Compounds on Rat Mesenteric Arteries

B. monnieri extract (BME) is an abundant source of bioactive compounds, including saponins and flavonoids known to produce vasodilation. However, it is unclear which components are the more effective vasodilators. The aim of this research was to investigate the vasorelaxant effects and mechanisms of action of saponins and flavonoids on rat isolated mesenteric arteries using the organ bath technique. The vasorelaxant mechanisms, including endothelial nitric oxide synthase (eNOS) pathway and calcium flux were examined. Saponins (bacoside A and bacopaside I), and flavonoids (luteolin and apigenin) at 0.1–100 µM caused vasorelaxation in a concentration-dependent manner. Luteolin and apigenin produced vasorelaxation in endothelial intact vessels with more efficacy (E(max) 99.4 ± 0.7 and 95.3 ± 2.6%) and potency (EC(50) 4.35 ± 1.31 and 8.93 ± 3.33 µM) than bacoside A and bacopaside I (E(max) 83.6 ± 2.9 and 79.9 ± 8.2%; EC(50) 10.8 ± 5.9 and 14.6 ± 5.4 µM). Pretreatment of endothelial intact rings, with L-NAME (100 µM); an eNOS inhibitor, or removal of the endothelium reduced the relaxant effects of all compounds. In K(+)-depolarised vessels suspended in Ca(2+)-free solution, these active compounds inhibited CaCl(2)-induced contraction in endothelial denuded arterial rings. Moreover, the active compounds attenuated transient contractions induced by 10 µM phenylephrine in Ca(2+)-free medium containing EGTA (1 mM). Thus, relaxant effects occurred in both endothelial intact and denuded vessels which signify actions through both endothelium and vascular smooth muscle cells. In conclusion, the flavonoids have about twice the potency of saponins as vasodilators. However, in the BME, there is ~20 × the amount of vaso-reactive saponins and thus are more effective.