文献类型：期刊文献

英文题名：Puerarin Suppresses Angiotensin II-Induced Cardiac Hypertrophy by Inhibiting NADPH Oxidase Activation and Oxidative Stress-Triggered AP-1 Signaling Pathways

作者：Chen, Gang[1];Cao, Qiang[2];Cui, Xiangli[1];Pan, Shifen[1];Shen, Chong[3,4];Liu, Lihong[1]

第一作者：Chen, Gang

通信作者：Liu, LH[1]

机构：[1]Capital Med Univ, Beijing Chao Yang Hosp, Beijing, Peoples R China;[2]Gansu Univ Chinese Med, Clin Coll Tradit Chinese Med, Lanzhou, Peoples R China;[3]Chinese Acad Med Sci, Inst Med Biotechnol, Beijing 100730, Peoples R China;[4]Peking Union Med Coll, Beijing 100021, Peoples R China

第一机构：Capital Med Univ, Beijing Chao Yang Hosp, Beijing, Peoples R China

通信机构：[1]corresponding author), Beijing Chao Yang Hosp, Dept Pharm, 8 Gongren Tiyuchang Nanlu, Beijing, Peoples R China.

年份：2015

卷号：18

期号：2

起止页码：235

外文期刊名：JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

收录：;Scopus(收录号：2-s2.0-84936856674);WOS:【SCI-EXPANDED(收录号:WOS:000357338600010)】；

基金：The work was supported by grants from the National S&T Major Special Project on Major New Drug Innovation (2012ZX09301002-001-015) and National Scientific Foundation of China (30772284).

语种：英文

摘要：To examine the effects of puerarin (Pue) on angiotensin II (AngII)-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and oxidative stress-related signaling pathways in the hypertrophic response of cardiomyocytes. METHODS. Primary cardiomyocytes of neonatal C57BL/6J mice were pretreated with Pue (50, 100 mu mol/L) and were then stimulated with AngII 1 mu mol/L. NADPH oxidase activity and reactive oxygen species (ROS) levels were measured by lucigenin-enhanced chemiluminescence assay and flow cytometry. Western blotting was used to detect the distribution of the oxidase subunits, extracellular signal-regulated kinase (ERK1/2) and c-jun N-terminal kinase (JNK1/2) activation, and an electrophoretic mobility shift assay (EMSA) was performed to analyze the DNA binding activity of activator protein-1 (AP-1). Adult C57BL/6J mice were infused with AngII and were administered with Pue (100, 200 mg.kg(-1).d(-1)) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were examined. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were measured, and heart morphometry was assessed. RESULTS. In vitro, Pue dose-dependently blocked the phosphorylation of ERK1/2 and JNK1/2 and eventually abolished AP-1 binding activity through the inhibition of ROS production. Further studies revealed that AngII treatment resulted in increased NADPH oxidase activity, which was suppressed by Pue via the disruption of Rac1 activation and membrane translocation of oxidase subunits. In vivo, Pue attenuated cardiac hypertrophy, as evaluated by decreased HW/BW, LVW/BW, myocyte surface area, and left ventricular wall thickness. CONCLUSIONS. The anti-hypertrophic mechanism of Pue occurred by blocking Rac1-dependent NADPH oxidase activation and downstream redox-sensitive AP-1 signaling pathways.