title: Inhibitory effects of 2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside on angiotensin II-induced proliferation of vascular smooth muscle cells.
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 G /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 <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.
authors: Department of Pharmacology, Nantong University Pharmacy College, Nantong, 226001, China.
authors: Xiao-le
authors: XL
authors: Xu
authors: Yan-juan
authors: YJ
authors: Huang
authors: Dan-yan
authors: DY
authors: Ling
authors: Wei
authors: W
authors: Zhang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005960:Glucosides; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000804:Angiotensin II; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases