1. Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts.
- Author
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Chan P, Liu JC, Lin LJ, Chen PY, Cheng TH, Lin JG, and Hong HJ
- Subjects
- Angiotensin II metabolism, Animals, Cells, Cultured, Drugs, Chinese Herbal chemistry, Endothelin-1 metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Heart drug effects, Myocardium metabolism, Myocardium pathology, Myofibroblasts metabolism, Myofibroblasts pathology, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type III metabolism, Phosphorylation, RNA, Small Interfering pharmacology, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Salvia miltiorrhiza chemistry, Signal Transduction drug effects, Transfection, Abietanes pharmacology, Angiotensin II antagonists & inhibitors, Antioxidants pharmacology, Cell Proliferation drug effects, Drugs, Chinese Herbal pharmacology, Myocardium cytology, Myofibroblasts drug effects
- Abstract
Tanshinone IIA extracted from danshen, a popular medicinal herb used in traditional Chinese medicine, exhibits cardio-protective effects. However, the mechanism of its cardioprotective effect is not well established. The aims of this study were to examine whether tanshinone IIA may alter angiotensin II (Ang II)-induced cell proliferation and to identify the putative underlying signaling pathways in rat cardiac fibroblasts. Cultured rat cardiac fibroblasts were pre-treated with tanshinone IIA and stimulated with Ang II, cell proliferation and endothelin-1 (ET-1) expression were examined. The effect of tanshinone IIA on Ang II-induced reactive oxygen species (ROS) formation, and extracellular signal-regulated kinase (ERK) phosphorylation were also examined. In addition, the effect of tanshinone IIA on nitric oxide (NO) production, and endothelial nitric oxide synthase (eNOS) phosphorylation were tested to elucidate the intracellular mechanism. The increased cell proliferation and ET-1 expression by Ang II (100 nM) were partially inhibited by tanshinone IIA. Tanshinone IIA also inhibited Ang II-increased ROS formation, and ERK phosphorylation. In addition, tanshinone IIA was found to increase the NO generation, and eNOS phosphorylation. N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, and the short interfering RNA transfection for eNOS markedly attenuated the inhibitory effect of tanshinone IIA on Ang II-induced cell proliferation. The results suggest that tanshinone IIA prevents cardiac fibroblast proliferation by interfering with the generation of ROS and involves the activation of the eNOS-NO pathway.
- Published
- 2011
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