Leonurine Alleviates Hypoxia-Induced Myocardial Damage by Regulating miRNAs

Abstract

Objective miRNAs as pharmaco-targets have been investigated in multifarious diseases. Our study aimed to determine whether leonurine was a potential cardioprotective agent by targeting miRNAs in hypoxia-stimulated mice and H9c2 cardiomyocytes. Methods Cell proliferation and apoptosis were examined by CCK-8 and TUNEL assay in hypoxia-stimulated rat H9c2 cardiomyocytes. miRNAs expression levels in cardiomyocytes in response to hypoxia stimulation were detected by RT-qPCR. Mice with myocardial injury were induced by chronic intermittent hypoxia stimulation. Results Leonurine alleviated hypoxia-induced cardiac hypertrophy in mice. Moreover, up-regulation of miR-31 and down-regulation of miR-210 in hypoxia-stimulated mice were reversed by leonurine administration. Leonurine exhibited cardioprotective activity in an vitro cell model of hypoxia-stimulated rat H9c2 cardiomyocytes, reflecting that the compound improved hypoxia-induced growth inhibition and apoptosis of cardiomyocytes. TUNEL assay revealed that transfection of miR-31 inhibitors or miR-210 mimics abrogated hypoxia-induced cardiomyocyte apoptosis. In contrast to that, miR-31 mimics or miR-210 inhibitors counteracted the anti-apoptotic effect of leonurine on hypoxia-treated rat H9c2 cardiomyocytes. Conclusion Our findings suggest that miR-31 and miR-210 as the upstream regulators of leonurine are involved in hypoxia-induced cardiomyocyte apoptosis. Leonurine can target miRNAs to protect against hypoxia-induced myocardial damage. miRNAs as potential drug targets may provide prospective therapeutic strategies for the treatment of myocardial damage.