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2,3,4′,5-tetrahydroxystilbene-2-0-β-D glucoside (TSG) has been recognized to suppress the proliferation of vascular smooth muscle cells (VSMCs).The aim of the present study was to determine whether TSG inhibits neointimal hyperplasia in a rat carotid arterial balloon injury model.Balloon injury was induced in the left common carotid artery of rats.TSG (30,60,120 mg·kg-1·d-1) was treated from 3 days prior to,until 14 days after the induction of balloon injury.The ratio of intima-to-media was significantly reduced in the TSG-treated rats at 14 days after the induction of injury,which was associated with reduced expressions of proliferating cell nuclear antigen (PCNA),α-smooth muscle actin (α-SMA) and platelet-derived growth factor-BB (PDGF-BB),as markers of VSMCs proliferation and migration.Additionally,TSG significantly inhibited PDGF-BB induced cell migration in cultured VSMCs.Furthermore,we explored the underlying mechanisms for such effects of TSG.The result showed that TSG markedly reduced balloon injury-induced AKT,ERK and NF-κB activation as well as mRNA expressions of c-myc,c-fos and c-jun,which is important signal pathway for VSMCs proliferation.And in both vivo and vitro model,TSG markedly regulated matrix metalloproteinase-2,9 expressions and collagen Ⅰ,Ⅲ expressions,which are key factors in extracellular matrix for VSMCs migration.These results suggest that the anti-proliferative and anti-migrative effects of TSG on VSMCs could help to explain the beneficial effects of TSG on neointima hyperplasia induced by balloon injury.