Garcinia cowa Leaf Ethanolic Extract Induces Vasorelaxation Through eNOS/NO/sGC Pathway, Potassium, and Calcium Channels in Isolated Rat Thoracic Ao

Abstract

Background: Garcinia cowa Roxb. ex Choisy (G. cowa) is used in traditional medicine, both for improvement of blood circulation and indigestion, also as an antipyretic and expectorant. Objective: This study investigated the vasorelaxant effects and possible mechanisms of action of G. cowa leaf ethanolic extract (GCE) on the rat isolated thoracic aorta. Methods: The study examined the effects of GCE on isolated rat thoracic aorta, including both endothelium-intact and endothelium-denuded aortic rings, using an organ bath system. Specific inhibitors were used to evaluate the mechanism involved in GCE-induced vasorelaxation. Results: GCE (0.01–10 mg/mL) relaxed endothelium-intact aortic rings, that had been precontracted with phenylephrine. Removal of the endothelium or pretreatment of endothelium-intact aortic rings with NꞶ-nitro-L-arginine methyl ester (L-NAME), or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), significantly decreased vasorelaxation induced by the GCE. Indomethacin or propranolol had no effect on the GCE-induced relaxation of the endothelium-intact aortic rings. In endothelium-denuded aortic rings, the relaxation effect of GCE was significantly blocked by 4-aminopyridine (4-AP) and tetraethylammonium (TEA) at the maximum dose of GCE, but not by glibenclamide. In Ca2+-free Krebs solution, GCE (5 and 10 mg/mL) significantly inhibited extracellular Ca2+ induced contraction in pre-contracted rings with high KCl levels. Conclusions: These findings suggest that GCE exhibits both an endothelium-dependent, which is mediated by an eNOS/NO/sGC pathway, and an endothelium-independent pathway, which involves KCa and KV channels opening and extracellular Ca2+ influx inhibition. Kaempferol, isovitexin, quercetin, apigenin, luteolin, and amentoflavone might play a role in inducing the vasorelaxant effect of GCE. Keywords: Garcinia cowa, Vasorelaxant effect, Endothelium, K+ channel, Ca2+ channel