ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1538091
This article is part of the Research TopicInnovative Approaches and Molecular Mechanisms in Cardiovascular PharmacologyView all 16 articles
Wenyang Zhenshuai Granules inhibits cardiomyocyte apoptosis in chronic heart failure by regulating p38 MAPK signaling pathway through exosomal miR-155
Provisionally accepted
- 1Hunan University of Chinese Medicine, Changsha, Anhui Province, China
- 2The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
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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 hours 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.
Keywords: chronic heart failure, exosome, miR-155, p38 MAPK, Cardiomyocyte apoptosis, Doxorubicin, Wenyang Zhenshuai Granules
Received: 02 Dec 2024; Accepted: 10 Sep 2025.
Copyright: © 2025 Peng, Chen, Cai, Tang, Chen and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qingyang Chen, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
Fang Zhou, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
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