@article{APS7737,
author = {Gang Chen and Shi-qi Pan and Cong Shen and Shi-fen Pan and Xiu-min Zhang and Qi-yang He},
title = {Puerarin inhibits angiotensin II-induced cardiac hypertrophy via the redox-sensitive ERK1/2, p38 and NF-κB pathways},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {4},
year = {2016},
keywords = {},
abstract = {Gang CHEN1, *, Shi-qi PAN2, Cong SHEN1, Shi-fen PAN3, Xiu-min ZHANG1, Qi-yang HE1, *
1Institute of Medicinal Biotechnology, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China; 2The 4th Affiliated Hospital of Harbin Medical University, Harbin 150001, China; 3Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
Aim: To investigate the effects of puerarin (Pue), an isoflavone derived from Kudzu roots, on angiotensin II (Ang II)-induced hypertrophy of cardiomyocytes in vivo and in vitro.
Methods: C57BL/6J mice were infused with Ang II and treated with Pue (100 mg·kg-1·d-1, po) for 15 d. After the treatment, systolic blood pressure (SBP) and left ventricular wall thickness were assessed. The ratios of heart weight to body weight (HW/BW) and left ventricular weight to body weight (LVW/BW) were determined, and heart morphometry was assessed. Expression of fetal-type genes (ANP, BNP and β-MHC) in left ventricles was measured using semi-quantitative RT-PCR. Mouse primary cardiomyocytes were treated with Pue (50, 100, 200 μmol/L), then exposed to Ang II (1 μmol/L). ROS level was examined with flow cytometry, the binding activity of NF-κB was determined using EMSA. Western blot was used to measure the levels of ERK1/2, p38 and NF-κB pathway proteins. [3H]leucine incorporation was used to measure the rate of protein synthesis.
Results: Oral administration of Pue significantly suppressed Ang II-induced increases in the myocyte surface area, HW/BW, LVW/BW, SBP and left ventricular wall thickness. Furthermore, Pue significantly suppressed Ang II-induced increases in ANP, BNP and β-MHC expression in the left ventricles in vivo. Treatment of cardiomyocytes with Pue (50–500 μmol/L) did not affect the viability of cardiomyocytes in vitro. Pretreatment of cardiomyocytes with Pue dose-dependently inhibited Ang II-induced increases in ROS production, NF-κB binding activity, protein synthesis and cell breadth. Furthermore, pretreatment with Pue significantly suppressed Ang II-induced activation of ERK1/2, p38 and the NF-κB pathway proteins and the expression of ANP and β-MHC in cardiomyocytes. The positive drug valsartan exerted similar effects on Ang II-induced cardiac hypertrophy in vivo and in vitro.
Conclusion: Pue attenuates Ang II-induced cardiac hypertrophy by inhibiting activation of the redox-sensitive ERK1/2, p38 and the NF-κB pathways.
Keywords: cardiac hypertrophy; angiotensin II; ROS; ERK1/2; p38; NF-κB; puerarin; isoflavone; Kudzu root; valsartan
The work was supported by grants from the National S&T Major Special Project on Major New Drug Innovation (2012ZX09301002-001-015) and the National Natural Science Foundation of China (81273553).
* To whom correspondence should be addressed.
E-mail chengang102009@126.com (Gang CHEN); qiyang_he@vip.163.com (Qi-yang HE)
Received 2013-08-29 Accepted 2013-11-27},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7737}
}