Enhancement of vascular relaxation in rat aorta by phytoestrogens from Curcuma comosa Roxb

The present study aims to examine the effects and mechanisms of Curcuma comosa Roxb., an indigenous medicinal plant containing phytoestrogens, on vascular relaxation. Using an organ bath system, acute exposure of intact or endothelium-denuded aortic rings to the hexane extract of C. comosa or an isolated diarylheptanoid compound, D3, did not induce relaxation. However, pre-incubation of aortic rings for 20 min with hexane extract of C. comosa (10 microg/ml) or the isolated diarylheptanoid compound, D3, (0.1, 1 and 10 microg/ml) markedly enhanced endothelial-dependent relaxation in response to ACh. The hexane extract did not modulate the relaxation of denuded aortic rings in response to SNP, which suggested a predominant effect on endothelial cells rather than on vascular smooth muscle cells. Co-incubation with ICI 182,780 (estrogen receptor antagonist), L-NAME (nitric oxide synthase inhibitor) or ODQ (guanylase cyclase inhibitor) inhibited the enhancing effects of C. comosa on ACh-induced relaxation. These findings suggest that the actions of C. comosa are mediated through estrogen receptor (ER) and NO-cGMP-dependent mechanisms. In addition, C. comosa also increased the phosphorylation of serine 1177 eNOS and serine 473 Akt proteins, and these effects were abolished by ICI 182,780. The results suggest that C. comosa acutely increases endothelium-dependent relaxation of aortic rings through the ER-Akt-eNOS pathway. This is the first evidence indicating non-genomic action of a novel phytoestrogen from C. comosa, on vascular relaxation.