Inhibitory effects of 2,3,4',5-tetrahydroxystilbene-2-O-β-D-glucoside on angiotensin II-induced proliferation of vascular smooth muscle cells

To investigate the effect of 2,3,4',5-tetrahydroxystilbene-2-O-beta-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. 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. 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). 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.