P13 Pinocembrin isolated from Propolis induces relaxation of rat basilar artery rings through both endothelium-dependent and -independent pathways

Objective: Pinocembrin (5,7-dihydroxyflavanone) is one of the primary flavonoids in propolis with various biological activities. We found that pinocembrin increased cerebral blood flow and improved the outcome after focal or global cerebral ischemia/reperfusion injury in rats. In the present study, the vasorelaxant effect of pinocembrin on the rat basilar artery and its potential mechanisms were studied. Methods: Endothelium-intact and -denuded basilar artery rings were prepared from SD rats, and then stimulated with KCl, 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1). The tension of the basilar artery rings was measured through an isometric force transducer. Results: Pinocembrin induced vasorelaxation in a dose-dependent manner in endothelium-intact rings contracted by KCl, 5-HT, and ET-1. However, partial loss of the vasorelaxation induced by pinocembrin was observed in endothelium-denuded rings contracted by KCl. The vasorelaxant effect of pinocembrin was significantly reduced by pre-incubation with the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME), the guanylate cyclase inhibitor ODQ and the cyclooxygenase inhibitor indomethacin. In addition, the pinocembrin-induced relaxations were remarkably attenuated by the voltage-dependent K + channel blocker 4-aminopyridine, the ATP-sensitive K + channel blocker glibenclamide and the Ca 2+ -activated K + channel blocker tetraethylammonium. Moreover, pre-incubation with pinocembrin dramatically suppressed the high K + -induced extracellular Ca 2+ influx and ET-1-induced intracellular Ca 2+ release in endothelium-denuded rings. Conclusion: These results demonstrated that pinocembrin has a vasorelaxant effect in isolated rat basilar artery rings. It may exert its effects by an endothelium-dependent pathway involving NO-cGMP, and also through an endothelium-independent pathway, opening K + channels and blockade of Ca 2+ channels.