Ginsenoside Rg3 improves microcystin-induced cardiotoxicity through the miR-128-3p/MDM4 axis

Abstract

Microcystin (MC) is the byproduct of cyanobacteria metabolism that is associated with oxidative stress and heart damage. This study aimed to investigate the effect of ginsenoside Rg3 on MC-induced cardiotoxicity. A mouse model of myocardial infarction was constructed by oral MC administration. H9C2 cells were used for in vitro analysis. Cellular oxidative stress, apoptosis, and the relationship between miR-128-3p and double minute 4 protein (MDM4) were analyzed. MiR-128-3p expression was upregulated in vitro and in vivo after MC treatment, which was downregulated after Rg3 treatment. Left ventricular ejection fraction (LVEF) and left ventricular systolic pressure (LVSP) were increased and left ventricular end–diastolic pressure (LVEDP) was decreased after Rg3 treatment. Moreover, Rg3 alleviated MC-induced pathological changes and apoptosis in myocardial tissues. Meanwhile, Rg3 treatment decreased the lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and inhabited cell apoptosis and oxidative stress in MC-treated myocardial cells. MiR-128-3p overexpression attenuated the protective effect of Rg3 on MC-induced cardiotoxicity. MiR-128-3p negatively regulated MDM4 expression. This study revealed that Rg3 alleviated MC-induced cardiotoxicity through the miR-128-3p/MDM4 axis, which emphasized the potential of Rg3 as a therapeutic agent for MC-induced cardiotoxicity, and miR-128-3p as a target for the Rg3 therapy.

Graphical Abstract

Keywords:

• Microcystin
• cardiomyocyte toxicity
• ginsenoside Rg3
• MiR-128-3p
• MDM4

Acknowledgments

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Ethical approval

All animal tests were approved by the Animal Ethics Committee of Changsha Health Vocational College.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data generated or analyzed during this study are included in this published article.

Additional information

Funding

This work was supported by the Hunan Natural Science Foundation-Kewei Joint Project ‘Discussion and Mechanism Study of Mitochondrial-related miRNAs in Microcystin-mediated Cardiotoxicity and Protective Effects of Ginseng’ (2020JJ8094).