title: Tanshinone IIA inhibits angiotensin II-induced cell proliferation in rat cardiac fibroblasts.
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.
authors.affiliation: Department of Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.forename: Ju-Chi
authors.initials: JC
authors.lastname: Liu
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lin
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Chen
authors.forename: Tzu-Hurng
authors.initials: TH
authors.lastname: Cheng
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.forename: Hong-Jye
authors.initials: HJ
authors.lastname: Hong
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D019332:Endothelin-1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D045784:Abietanes; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C021751:tanshinone; D000804:Angiotensin II; C028972:dan-shen root extract; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D048049:Extracellular Signal-Regulated MAP Kinases; D019331:NG-Nitroarginine Methyl Ester