Notoginsenoside R1 inhibits Ang II-induced VSMCs migration by upregulating Sirt1 expression

Abstract Objectives To investigate whether Notoginsenoside R1 (NGR1) inhibits angiotensin II (Ang II)-induced vascular smooth muscle cells (VSMCs) migration and to elucidate the underlying mechanisms. Methods VSMCs migration model were established using 1 μM Ang II treatment. Subsequently, the migration VSMCs were treated with varying concentrations of NGR1 (0, 10, 20, and 40 μM), respectively. A scratch wound assay was performed to assess the migration area of VSMCs, and western blotting assay was used to evaluate the levels of matrix metalloproteinases (MMP-2, MMP-9), p38 MAPK, phosphorylated p38 MAPK, and silent information regulator 1 (Sirt1) proteins. Results NGR1 inhibited Ang II-induced VSMCs migration, downregulated migration-related proteins MMP-2, MMP-9, and p38 MAPK phosphorylation, while upregulating Sirt1 in a dose-dependent manner. Furthermore, upregulation Sirt1 effectively inhibited Ang II-induced VSMCs migration and reduced p38 MAPK phosphorylation proteins expression. Notably, upregulation Sirt1 also further enhanced the inhibitory effects of NGR1 on VSMCs migration and decreased MMP-2, MMP-9, and p38 MAPK phosphorylation proteins expression. Conversely, Sirt1 silencing attenuated these effects. Conclusions NGR1 inhibits Ang II-induced migration of VSMCs by upregulating Sirt1, which suppresses p38 MAPK phosphorylation, MMP-2 and MMP-9 levels. These findings suggest that NGR1 may serve as a potential therapeutic agent for atherosclerosis.