ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>
Subject(s)
Animals , Male , Angiotensin II , Pharmacology , Cell Cycle , Cell Proliferation , Extracellular Signal-Regulated MAP Kinases , Metabolism , Glucosides , Pharmacology , Intracellular Space , Metabolism , Mitogen-Activated Protein Kinase Kinases , Metabolism , Muscle, Smooth, Vascular , Cell Biology , Myocytes, Smooth Muscle , Cell Biology , Phosphorylation , Proliferating Cell Nuclear Antigen , Metabolism , Proto-Oncogene Proteins , Metabolism , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Reactive Oxygen Species , Metabolism , Stilbenes , Pharmacology , Superoxide Dismutase , MetabolismABSTRACT
<p><b>AIM</b>To observe the changes of MMP-2, 9 level on atherosclerosis in experimental rats by treatment of 2,3,4',5-tetrahydroxystilbene-2-0-beta-D glucoside (TSG) and to investigate the mechanism of TSG in stabilizing plaque and anti-atherosclerosis.</p><p><b>METHODS</b>The atherosclerosis model of rat was made by feeding high grease food and injecting VitD3. Sixty male SD rats were randomly divided into six groups: control, Simvastatin, model and TSG 120 mg x kg(-1) x d(-1), TSG 60 mg x kg(-1) x d(-1) and TSG 30 mg x kg(-1) x d(-1). After 12 weeks, several aorta were randomly tested, model and TSG 120 mg x kg(-1) x d(-1), TSG 60 mg kg(-1) x d(-1) and TSG 30 mg x kg(-1) x d(-1). After 12 weeks, several aorta were randomly tested, model made was successful when we found plaque. And after six weeks treating, the mRNA expressions of MMP-2 and MMP-9 were measured by RT-PCR. The activities of MMP-2 and MMP-9 were measured by Western blot. The levels of CRP, IL-6 and TNF-alpha in serum were measured in biochemical method.</p><p><b>RESULTS</b>Data of the study demonstrated that the level of TNF-alpha, IL-6, CRP, MMP-2 and MMP-9 were remarkably decreased by TSG60, 120 mg x kg(-1) x d(-1) groups, which showed a dose-dependent effect.</p><p><b>CONCLUSION</b>TSG has the effect of anti-atherogenic and stabilizing plaque on the experimental rats with atherosclerosis, which are induced by the high cholesterol feeding and VitD3 injecting. The effect of TSG seems to be closely involved in regulating the expressions of MMP-2 and MMP-9, and inhibiting inflammation.</p>