Wenyang Zhenshuai Granules inhibits cardiomyocyte apoptosis in chronic heart failure by regulating p38 MAPK signaling pathway through exosomal miR-155

Background: Chronic heart failure (CHF) represents a significant global public health concern, warranting further investigation and intervention. Wenyang Zhenshuai Granules (WZG) is an in-hospital preparation of the First Affiliated Hospital of Hunan University of Chinese Medicine, which has been approved by the Hunan Provincial Drug Administration (Approval No.: Z20190105000) for the treatment of CHF. The objective of this study was to examine the impact of WZG on cardiomyocyte apoptosis in CHF through the regulation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway by exosomal microRNA-155. Methods: Doxorubicin (DOX) was employed to construct a model of cardiomyocyte injury associated with CHF. The H9c2 cells were divided into four groups: the normal control group (NC), the DOX group (DOX), the DOX + drug-containing serum group (DOX+WZG), and the DOX + enalapril (ENP) group (DOX+ENP). The morphology of the cardiomyocytes was observed at 15, 30, and 45 h into the experiment using an inverted microscope. The viability of cells and the number of apoptotic cells were determined through the use of a CCK-8 assay and flow cytometry, respectively. Subsequently, exosomes were extracted and subjected to morphological characterization and identification. The expression of exosomal miR-155, the p38 MAPK signaling pathway, and apoptotic proteins were examined. Results: The results demonstrated that WZG could enhance the morphology of H9c2 cells, diminish the apoptosis rate of cells, and augment the viability of cells. Western blot and RT-qPCR assays provided further confirmation that WZG could promote the secretion of exosomes from cardiomyocytes, increase the content of miR-155 in exosomes, and inhibit the activation of the p38 MAPK signaling pathway. Conclusion: WZG inhibits p38 MAPK protein phosphorylation via exosomal miR-155, thereby exerting anti-apoptotic effects on cardiomyocytes in CHF.