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Inhibitory Effects of 2,3,4',5-tetrahydroxystilbene-2-O-β- D-glucoside on Angiotensin Ⅱ-Induced Proliferation of Vascular Smooth Muscle Cells
  
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KeyWord:2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside, vascular smooth muscle cells, proliferation, angiotensin Ⅱ, Chinese medicine Polygonum multiflorum
Author NameAffiliationE-mail
XU Xiao-le, HUANG Yan-juan, LING Dan-yan   
ZHANG Wei Department of Pharmacology, Nantong University Pharmacy College, Nantong (226001), China weizhangntu@yahoo.com 
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Abstract:
      Objective: To investigate the effect of 2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from the root of Polygonum multiflorum, on angiotensin Ⅱ (Ang Ⅱ)-induced proliferation of cultured rat vascular smooth muscle cells (VSMCs) and to identify the potential mechanism. Methods: Cell proliferation and cell cycle were determined by cell counting, 5-bromo-2'-deoxyuridine incorporation assay, proliferating cell nuclear antigen protein expression and flow cytometry. Levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), mitogenic extracellular kinase 1/2 (MEK1/2) and Src in VSMCs were measured by Western blot. The expression of c-fos, c-jun and c-myc mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). Intracellular reactive oxygen species (ROS) was measured by fluorescence assay. Results: TSG significantly inhibited Ang Ⅱ-induced VSMCs proliferation and arrested cells in the G1/S checkpoint (P<0.05 or P<0.01). TSG decreased the levels of phosphorylated ERK1/2, MEK1/2 and Src in VSMCs (P<0.05 or P<0.01). TSG also suppressed c-fos, c-jun and c-myc mRNA expression (P<0.05 or P<0.01). In addition, the intracellular ROS was reduced by TSG (P<0.01). Conclusions: TSG inhibited Ang Ⅱ-induced VSMCs proliferation. Its antiproliferative effect might be associated with down-regulation of intracellular ROS, followed by the suppression of the Src-MEK1/2-ERK1/2 signal pathway, and hence, blocking cell cycle progression.
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