Notoginsenoside R1 from Panax notoginseng inhibits TNF-alpha-induced PAI-1 production in human aortic smooth muscle cells.

Notoginsenoside R1 is the main ingredient with cardiovascular activity in Panax notoginseng. We reported that notoginsenoside R1 significantly decreased tumor necrosis factor-alpha (TNF-alpha)-induced plasminogen activator inhibitor-1 (PAI-1) mRNA, protein level and secretion in human aortic smooth muscle cells (HASMCs) in a dose-dependent manner. TNF-alpha significantly increased extracellular signal-related kinases (ERK) and protein kinase B (PKB) activation and, which was blocked by notoginsenoside R1, PD098059, U0126 or wortmannin. Our data demonstrates that TNF-alpha-induced up-regulation of PAI-1 mRNA and protein levels and secretion occur via activation of ERK and PKB, which was prevented by treatment of notoginsenoside R1, PD098059, U0126 or wortmannin. These results suggest that notoginsenoside R1 inhibits TNF-alpha-induced PAI-1 overexpression in HASMCs by suppressing ERK and PKB signaling pathways.