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.
Zhang
Hong-Sheng
HS
Department of Biotechnology, Beijing Institute of Radiation Medicine, Taiping Road 27#, Haidian District, Beijing 100850, P R China.
Wang
Sheng-Qi
SQ
D000730:Androstadienes / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology; D005894:Panax / Q000737:chemistry*; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000077191:Wortmannin
D000730:Androstadienes; D036145:Ginsenosides; D017395:Plasminogen Activator Inhibitor 1; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C051321:SERPINE1 protein, human; D014409:Tumor Necrosis Factor-alpha; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D000077191:Wortmannin; C072936:notoginsenoside R1