Tetrahydroxystilbene Glucoside Improves TNF-alpha-Induced Endothelial Dysfunction: Involvement of TGF beta/Smad Pathway and Inhibition of Vimentin Expression

摘要

Endothelial dysfunction plays an important role in the pathogenesis of atherogenesis. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum (PM), exhibits significant anti-atherosclerotic activity. Here, we used human umbilical vein endothelial cells (HUVECs) induced by tumor necrosis factor-alpha (TNF-alpha) in vitro to investigate the cytoprotective effects of TSG on TNF-alpha-induced endothelial injury and the related mechanisms. Pretreatment with 50 and 100 mu M TSG markedly attenuated TNF-alpha-induced loss of cell viability and release of lactate dehydrogenase (LDH) and inhibited TNF-alpha-induced cell apoptosis. The inhibition of vimentin expression was involved in the cytoprotection afforded by TSG. Using inhibitors for PI3K and TGF beta or siRNA for Akt and Smad2, we found that vimentin production in HUVECs is regulated by TGF beta/Smad signaling, but not by PI3K-Akt-mTOR signaling. Meanwhile, TSG inhibited both the expression of TGF beta 1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by TNF-alpha. These results suggest that TSG protects HUVECs against TNF-alpha-induced cell damage by inhibiting vimentin expression via the interruption of the TGF beta/Smad signaling pathway.