Article

Puerarin ameliorated pressure overload-induced cardiac hypertrophy in ovariectomized rats through activation of the PPARα/PGC-1 pathway

Authors: Ning Hou1,2, Yin Huang1,3, Shao-ai Cai1, Wen-chang Yuan2, Li-rong Li1,2, Xia-wen Liu1,2, Gan-jian Zhao1, Xiao-xia Qiu2, Ai-qun Li4, Chuan-fang Cheng1, Shi-ming Liu1, Xiao-hui Chen1, Dao-feng Cai2, Jing-xuan Xie3, Min-sheng Chen5, Cheng-feng Luo1
1 uangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China
2 ey Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
3 iangtan Central Hospital, Xiangtan 411100, China
4 anfang College of SUN YAT-SEN University, Guangzhou 510970, China
5 uangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
Correspondence to: Min-sheng Chen: gzminsheng@vip.163.com, Cheng-feng Luo: rocenphone@gzhmu.edu.cn,
DOI: 10.1038/s41401-020-0401-y
Received: 21 September 2019
Accepted: 16 March 2020
Advance online: 5 June 2020

Abstract

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg−1 ·d−1, ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 μM), which was attenuated by co- treatemnt with puerarin (100 μM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 μM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.
Keywords: cardiac hypertrophy; puerarin; ovariectomy; abdominal aortic constriction; PPARα

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