Inhibition of miRNA-1-Mediated Inflammation and Autophagy by Astragaloside IV Improves Lipopolysaccharide-Induced Cardiac Dysfunction in Rats

J Inflamm Res. 2022 Apr 23:15:2617-2629. doi: 10.2147/JIR.S362368. eCollection 2022.

Abstract

Introduction: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS).

Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels.

Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS.

Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.

Keywords: astragaloside IV; autophagy; cardiac dysfunction; inflammation; lipopolysaccharides; miRNA-1.

Grants and funding

This study was supported by National Natural Science Foundation of China (81960673, 81870329); the Key Projects of Natural Science Foundation of Liaoning Province (No. 20170540358); Project for Young Scientists Fund of Education Department of Liaoning Province (No. JYTQN201706); Natural Science Foundation of Gansu Province (21JR1RA135); Cuiying Technological Innovation Foundation of Lanzhou University Second Hospital (CY2019-MS03); Industrial Support Program for Colleges and Universities in Gansu Province (2020C-04); Special Research Project of Lanzhou University Serving the Economic and Social Development of Gansu Province (054000282).