title: The cardioprotection of dihydrotanshinone I against myocardial ischemia-reperfusion injury via inhibition of arachidonic acid ω-hydroxylase.
abstract: Arachidonic acid (AA) is a precursor that is metabolized by several enzymes to many biological eicosanoids. Accumulating data indicate that the ω-hydroxylation metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), is considered to be involved in the myocardial ischemia-reperfusion injury (MIRI). The inhibitors of AA ω-hydroxylase, however, are demonstrated to exhibit protective effects on MIRI. Dihydrotanshinone I (DI), a bioactive constituent of danshen, is proven to be a potent inhibitor of AA ω-hydroxylase by our preliminary study in vitro. The purpose of the present study was to investigate the cardioprotection of DI against MIRI and its effects on the concentrations of 20-HETE in vivo. Rats subjected to 30 min of ischemia followed by 24 h of reperfusion were assigned to intravenously receive vehicle (sham and ischemia-reperfusion), low (1 mg/kg), middle (2 mg/kg), or high (4 mg/kg) doses of DI before reperfusion. The results demonstrated that DI treatment could improve cardiac function, reduce infarct size, ameliorate the variations in myocardial zymogram and histopathological disorders, decrease 20-HETE generation, and regulate apoptosis-related protein in myocardial ischemia-reperfusion rats. These findings suggested DI could exert considerable cardioprotective action on MIRI by the attenuation of 20-HETE generation, subsequent myocardial injury, and apoptosis through inhibition on AA ω-hydroxylase.
authors: a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.
authors: Yidan
authors: Y
authors: Wei
authors: a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.|b Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, Jiangsu, China.
authors: Meijuan
authors: M
authors: Xu
authors: a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.
authors: Yi
authors: Y
authors: Ren
authors: a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.
authors: Guo
authors: G
authors: Lu
authors: a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.
authors: Yangmei
authors: Y
authors: Xu
authors: a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.
authors: Yangyang
authors: Y
authors: Song
authors: a State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, Jiangsu, China.
authors: Hui
authors: H
authors: Ji
mesh_terms: D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza
chemical_list: D045784:Abietanes; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; C021751:tanshinone; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; C409986:cytochrome P-450 omega-hydroxylase
keywords: 20-hydroxyeicosatetraenoic acid; acide 20-hydroxyéicosatétraénoïque; acide arachidonique; apoptose; apoptosis; arachidonic acid; danshen; dihydrotanshinone I; dommage d’ischémie–reperfusion myocardique; myocardial ischemia–reperfusion injury; ω-hydroxylase