Molecular targets and mechanisms of resveratrol in alleviating arrhythmia based on network pharmacology and bioinformatics

Background Arrhythmia refers to a disorder in which abnormal cardiac electrical activity leads to irregular heart rhythm and conduction. Resveratrol (Res), a natural polyphenol compound extracted from medicinal plants, plays an important role in the treatment of arrhythmia, but its precise molecular mechanisms remain unclear. Results The intersection of Res targets and arrhythmia yielded 78 common targets, including F-box protein 32 (FBXO32). These targets were significantly enriched in cardiac conduction system development, protein-containing complex, vascular endothelial growth factor (VEGF) signaling pathway, cyclic adenosine monophosphate (cAMP) signaling pathway, and forkhead box O (FoxO) signaling pathway. Molecular docking confirmed that FBXO32 could stably bind to Res. Res treatment increased cell viability in the arrhythmia cell model. FBXO32 was highly expressed in the arrhythmia cell model, but its expression was significantly reduced under Res treatment. Knockdown of FBXO32 increased cell viability, decreased apoptosis, and increased protein levels of calcium voltage-gated channel subunit alpha1 C (CACNA1C) and human ether-à-go-go-related gene (hERG), whereas Res treatment partially modulated these effects. Conclusions Res inhibits the expression of FBXO32, thereby suppressing the malignant phenotypes of arrhythmia.