PMID- 16713603 OWN - NLM STAT- MEDLINE DCOM- 20061027 LR - 20171116 IS - 0022-2828 (Print) IS - 0022-2828 (Linking) VI - 41 IP - 1 DP - 2006 Jul TI - Salvianolic acid B from Salvia miltiorrhiza inhibits tumor necrosis factor-alpha (TNF-alpha)-induced MMP-2 upregulation in human aortic smooth muscle cells via suppression of NAD(P)H oxidase-derived reactive oxygen species. PG - 138-48 AB - Activated matrix metalloproteinases (MMPs) in patients with acute coronary syndromes may contribute to plaque destabilization. Tumor necrosis factor-alpha (TNF-alpha) enhances NAD (P) H oxidase-dependent reactive oxygen species (ROS) formation and ROS induce MMP-2. In the present study, the effects of a potent water-soluble antioxidant, salvianolic acid B (SalB), derived from a Chinese herb, Salvia miltiorrhiza, on the expression of MMP-2 by TNF-alpha-treated human aortic smooth muscle cells (HASMCs) were investigated. In this study, salvianolic acid B scavenged H2O2 in a dose-dependent manner in test tube. We found that SalB, as well as NADPH oxidase inhibitors, DPI or apocynin, and antioxidant NAC, inhibited TNF-alpha-induced MMP-2 mRNA, protein expression, and gelatinolytic activity in HASMCs in a concentration-dependent manner. We also observed a dose-dependent decrease in ROS production and NADPH oxidase activity induced by TNF-alpha in the presence of SalB. SalB also significantly inhibited angiotensin II or H2O2-induced MMP-2 mRNA and protein expression and gelatinolytic activity in HASMCs. Our data point out that the importance of NADPH oxidase-dependent ROS generation in the control of SalB inhibition of TNF-alpha-induced MMP-2 expression and activity. FAU - Zhang, Hong-Sheng AU - Zhang HS AD - Department of Biotechnology, Beijing Institute of Radiation Medicine, Taiping Road 27#, Haidian District, Beijing 100850, China. FAU - Wang, Sheng-Qi AU - Wang SQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060519 PL - England TA - J Mol Cell Cardiol JT - Journal of molecular and cellular cardiology JID - 0262322 RN - 0 (Acetophenones) RN - 0 (Benzofurans) RN - 0 (Onium Compounds) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Necrosis Factor-alpha) RN - 11128-99-7 (Angiotensin II) RN - 6HJ411TU98 (diphenyleneiodonium) RN - B6J7B9UDTR (acetovanillone) RN - BBX060AN9V (Hydrogen Peroxide) RN - C1GQ844199 (salvianolic acid B) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetophenones/pharmacology MH - Acetylcysteine/pharmacology MH - Angiotensin II/metabolism/pharmacology MH - Aorta/cytology MH - Benzofurans/*pharmacology MH - Cells, Cultured MH - Humans MH - Hydrogen Peroxide/metabolism MH - Matrix Metalloproteinase 2/drug effects/genetics/*metabolism MH - Muscle, Smooth, Vascular/*drug effects/metabolism MH - NADPH Oxidases/drug effects/metabolism MH - Onium Compounds/pharmacology MH - Reactive Oxygen Species/*metabolism MH - Salvia miltiorrhiza/chemistry MH - Tumor Necrosis Factor-alpha/metabolism/*pharmacology MH - Up-Regulation EDAT- 2006/05/23 09:00 MHDA- 2006/10/28 09:00 CRDT- 2006/05/23 09:00 PHST- 2005/12/08 00:00 [received] PHST- 2006/01/22 00:00 [revised] PHST- 2006/03/14 00:00 [accepted] PHST- 2006/05/23 09:00 [pubmed] PHST- 2006/10/28 09:00 [medline] PHST- 2006/05/23 09:00 [entrez] AID - S0022-2828(06)00079-4 [pii] AID - 10.1016/j.yjmcc.2006.03.007 [doi] PST - ppublish SO - J Mol Cell Cardiol. 2006 Jul;41(1):138-48. doi: 10.1016/j.yjmcc.2006.03.007. Epub 2006 May 19.