2,3,4',5-tetrahydroxystilbene-2-O-ß-D-glucoside inhibits proliferation of vascular smooth muscle cells: involvement of NO/cGMP/PKG pathway.

ABSTRACT

The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. 2,3,4',5-Tetrahydroxystilbene-2-O-ß-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, has been found to have an antiatherosclerotic effect. The aim of this study was to investigate the effects of TSG on platelet derived growth factor (PDGF)-BB induced VSMCs proliferation and to explore the possible mechanisms of such effects. Pretreatment of VSMCs with TSG significantly inhibited PDGF-BB-induced cell proliferation in a concentration-dependent but not time-dependent manner. In addition, flow cytometry analysis of the DNA content revealed blocking of the PDGF-BB-inducible cell cycle progression by TSG. On the contrary, an inhibitory effect of TSG on VSMCs proliferation and expression of cell cycle regulators were markedly attenuated by addition of an nitric oxide (NO) synthase inhibitor, a soluble guanylate cyclase inhibitor and a cyclic GMP (cGMP)-dependent protein kinase (PKG) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4] oxadiazolo [4,3-α] quinoxalin-1-one (ODQ) and KT5823, respectively. It was also demonstrated that TSG enhanced NO and cGMP formation through up-regulating endothelial NO synthase expression in VSMCs. The findings indicate that TSG inhibited VSMCs proliferation induced by PDGF-BB may involve the NO/cGMP/PKG signal pathway.