J Appl Biomed 23:63-79, 2025 | DOI: 10.32725/jab.2025.007

Berberine improves atrial remodeling by regulating the AMPK/PPARα signaling pathway in a rabbit model of atrial fibrillation

Yang Wang *a, Zhe Suna, Zong-tao Yin, Jian Zhang, Fang-ran Xin, Yin-li Xu, Huai Lan
General Hospital of Northern Theater Command, Department of Cardiovascular Surgery, Shenyang, Liaoning, China

Atrial fibrillation (AF) is a common arrhythmia encountered in clinical practice, characterized by myocardial fibrosis and atrial remodeling as its primary pathological features, and associated with significantly high mortality and disability rates. Currently, there are no specific pharmacological treatments for AF, and traditional anti-arrhythmic drugs have not achieved the desired efficacy, often resulting in a high incidence of adverse drug reactions. Thus, there is an urgent need for the development of novel anti-AF medications. Berberine, the main active component of Coptis chinensis, has been shown to have antiarrhythmic and anti-heart failure effects. However, its potential to improve atrial fibrosis and remodeling resulting from AF remains largely unexplored. In this study, we used a rapid atrial pacing (RAP) procedure to establish a rabbit model of AF associated with atrial fibrosis. Our objective was to assess the inhibitory effects of berberine on myocardial fibrosis, evaluate its impact on atrial remodeling, and investigate its underlying molecular mechanisms. Our findings indicate that berberine reduces left atrial weight and the area of myocardial fibrosis, inhibits the expression of α-SMA protein in atrial tissue, and decreases the levels of inflammation and oxidative stress. In addition, berberine effectively inhibits atrial remodeling, which may contribute to the prevention of AF. Through transcriptomics, molecular docking, and molecular dynamics simulations, we have tentatively confirmed that berberine may activate the AMPK-PPARα signaling pathway by directly binding to AMPK and PPARα, thereby improving atrial fibrillation.

Keywords: AMPK-PPARα pathway; Atrial fibrillation; Atrial remodeling; Berberine; Rapid atrial pacing
Grants and funding:

This research was supported by the Natural Science Foundation of Liaoning Province (No. 2024-MS-251).

Conflicts of interest:

The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Received: January 9, 2025; Revised: May 8, 2025; Accepted: May 26, 2025; Prepublished online: May 27, 2025; Published: June 27, 2025  Show citation

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Wang Y, Sun Z, Yin Z, Zhang J, Xin F, Xu Y, Lan H. Berberine improves atrial remodeling by regulating the AMPK/PPARα signaling pathway in a rabbit model of atrial fibrillation. J Appl Biomed. 2025;23(2):63-79. doi: 10.32725/jab.2025.007. PubMed PMID: 40583339.
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