ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Shen-Yuan-Dan Capsule Inhibits METTL3-mediated m6A methylation to Restore Autophagy Homeostasis and Attenuate Post-Myocardial Infarction Heart Failure
Provisionally accepted
- Beijing Hospital of Traditional Chinese Medicine, Beijing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Heart failure (HF) after myocardial infarction (MI) is a serious health issue. This study investigates the therapeutic effects of Shen-Yuan-Dan Capsule (SYD) on post-MI HF and explores its mechanisms, particularly involving m6A modification and autophagy. Methods: Network pharmacology and MeRIP-seq were used to predict potential targets. A murine model of post-MI HF was established by ligating the left anterior descending artery in C57BL/6J mice, which were treated with SYD for 6 weeks. Cardiac function, autophagy-related proteins, m6A methylation, and METTL3 levels were assessed. In vitro, H9c2 cardiomyocytes were treated with Phenylephrine (PE) and SYD for 24 hours, and hypertrophic biomarkers, autophagy proteins, and m6A methylation were measured. METTL3-overexpressing H9c2 cells were also used to investigate SYD's effects on gene expression. Results: In vivo, SYD treatment significantly improved cardiac function in MI mice, including reduced cardiac hypertrophy, enhanced ejection fraction (EF) and fractional shortening (FS), and alleviated myocardial damage, fibrosis, and HF biomarkers. In vitro, SYD inhibited PE-induced hypertrophy in H9c2 cells, including a reduction in cell surface area and a decrease in hypertrophic biomarker levels. SYD also inhibited m6A methylation and METTL3 expression. In both MI mice and PE-treated H9c2 cells, SYD lowered m6A levels and METTL3 expression. Bioinformatics analysis identified autophagy-related signaling pathways. Electron microscopy and autophagy marker detection in myocardial tissue and H9c2 cells showed that SYD restored autophagy levels by regulating the mTOR/TFEB autophagy pathway. In METTL3-overexpressing H9c2 cells, SYD treatment reversed the hypertrophy induced by METTL3 overexpression. Conclusion: SYD alleviates post-MI HF by regulating the mTOR/TFEB autophagy pathway through inhibition of METTL3-mediated m6A modification.
Keywords: Autophagy, Heart Failure, Myocardial Infarction, N6-Methyladenosine, TraditionalChinese Medicine
Received: 08 Jul 2025; Accepted: 05 Feb 2026.
Copyright: © 2026 Guo, Chen, Xie, Li, Liu, Zhang, Liu 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:
Shuai-jie Guo
Ming-xue Zhou
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.