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Momordicine I alleviates isoproterenol-induced cardiomyocyte hypertrophy through suppression of PLA2G6 and DGK-ζ

  • Hongming Li (School of Pharmacy, Jiangxi Science & Technology Normal University) ;
  • Yumei Qiu (School of Pharmacy, Jiangxi Science & Technology Normal University) ;
  • Mengdie Xie (School of Pharmacy, Jiangxi Science & Technology Normal University) ;
  • Changsheng Ouyang (Department of Cardiology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University) ;
  • Xiaoyun Ding (School of Pharmacy, Jiangxi Science & Technology Normal University) ;
  • Hao Zhang (School of Pharmacy, Jiangxi Science & Technology Normal University) ;
  • Wei Dong (Key Laboratory of Modern Preparation of Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine) ;
  • Yinhua Xiong (School of Pharmacy, Jiangxi Science & Technology Normal University) ;
  • Xilan Tang (School of Pharmacy, Jiangxi Science & Technology Normal University)
  • Received : 2022.08.18
  • Accepted : 2022.09.23
  • Published : 2023.01.01

Abstract

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, βmyosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 ㎍/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy. Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ

Keywords

Acknowledgement

This work was supported by the grants from the National Natural Science Foundation of China (Nos.81960732, 82060733), Natural Science Foundation of Jiangxi Province (2018BAB215041), Startup Foundation for Doctors of Jiangxi Science & Technology Normal University (Nos.2017BSQD017), Open Project of Jiangxi Provincial Key Laboratory of Drug Design and Evaluation (JKLDE-KF-2101), and Open Project of Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Chinese Medicine (TCM-201911).

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