Natural products alleviate atrial fibrillation by modulating mitochondrial quality control

Atrial fibrillation (AF), one of the most common cardiac arrhythmias, is associated with high mortality rates and significant healthcare burdens. Mitochondrial homeostasis has recently emerged as a critical factor in AF pathogenesis but remains at the experimental stage. Current drug and surgical treatments for AF often involve side effects and require ongoing treatment plan evaluation and adjustment. In contrast, natural products (NPs), which have been utilized in China for over 2,000 years, show remarkable efficacy in treating AF and are receiving growing attention.

We aimed to investigate the regulatory effects of NPs on mitochondrial quality control (MQC) and their impact on AF occurrence and progression. By constructing a novel NP-mitochondria-AF axis, we propose a framework to translate experimental findings into clinical practice and identify potential therapeutic strategies for AF.

Databases such as PubMed, Web of Science, and China National Knowledge Infrastructure were searched (up to October 2024) using the following keywords: "atrial fibrillation," "traditional Chinese medicine," "mitochondrial biogenesis," "mitochondrial dynamics," "mitophagy," "apoptosis," "oxidative stress," "inflammation," and "Ca²⁺ concentration." NP targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, while disease targets were retrieved from Online Mendelian Inheritance in Man, GeneCards, and Therapeutic Target Database. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the Metascape database. Protein-protein interactions were analyzed using the STRING database, and core monomers and hub genes were identified using Cytoscape 3.7.2.

We found a strong relationship between mitochondrial homeostasis and AF development. KEGG pathway analysis indicated that commonly used NPs regulate mitochondrial homeostasis, affecting AF progression through various hub genes, including protein kinase B-alpha (AKT1), jun proto-oncogene (JUN), and tumor necrosis factor (TNF). Molecular docking analysis revealed that NP core monomers exhibited binding affinities to hub genes below -5 kcal/mol and to transforming growth factor-β (TGF-β) below -7 kcal/mol.

NPs, including traditional Chinese medicine (TCM) compounds, TCM monomers, and traditional Chinese patent medicines, alleviate AF by modulating MQC with minimal side effects and high efficacy. These findings highlight the therapeutic potential of NPs as promising candidates for AF treatment and further underscore the importance of MQC in AF pathogenesis.