Tetrahydroxystilbene glucoside improves TNF-α-induced endothelial dysfunction: involvement of TGFβ/Smad pathway and inhibition of vimentin expression

Am J Chin Med. 2015;43(1):183-98. doi: 10.1142/S0192415X15500123. Epub 2015 Jan 8.


Endothelial dysfunction plays an important role in the pathogenesis of atherogenesis. 2,3,5,4'-tetrahydroxystilbene-2-O-β-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-α (TNF-α) in vitro to investigate the cytoprotective effects of TSG on TNF-α-induced endothelial injury and the related mechanisms. Pretreatment with 50 and 100 μM TSG markedly attenuated TNF-α-induced loss of cell viability and release of lactate dehydrogenase (LDH) and inhibited TNF-α-induced cell apoptosis. The inhibition of vimentin expression was involved in the cytoprotection afforded by TSG. Using inhibitors for PI3K and TGFβ or siRNA for Akt and Smad2, we found that vimentin production in HUVECs is regulated by TGFβ/Smad signaling, but not by PI3K-Akt-mTOR signaling. Meanwhile, TSG inhibited both the expression of TGFβ1 and the phosphorylation of Smad2 and Smad3, and TSG suppressed the nuclear translocation of Smad4 induced by TNF-α. These results suggest that TSG protects HUVECs against TNF-α-induced cell damage by inhibiting vimentin expression via the interruption of the TGFβ/Smad signaling pathway.

Keywords: 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside; Endothelial Dysfunction; TGFβ Signaling; Tumor Necrosis Factor-α; Vimentin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Apoptosis / drug effects
  • Atherosclerosis / etiology
  • Cells, Cultured
  • Cytoprotection / drug effects
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Female
  • Gene Expression Regulation, Developmental / drug effects*
  • Glucosides / administration & dosage
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Polygonum / chemistry*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Smad Proteins / metabolism
  • Smad Proteins / physiology*
  • Stilbenes / administration & dosage
  • Stilbenes / isolation & purification
  • Stilbenes / pharmacology*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / physiology*
  • Tumor Necrosis Factor-alpha / adverse effects*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Umbilical Veins
  • Vimentin / metabolism*


  • Glucosides
  • Smad Proteins
  • Stilbenes
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Vimentin
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • L-Lactate Dehydrogenase