Plant-derived compounds as potential candidates for atrial fibrillation drug discovery: A review on phytochemicals with atrial-selective activity

OBJECTIVES: Atrial fibrillation (AF), the most prevalent type of cardiac arrhythmia, is associated with high morbidity and mortality. The pharmacological management of AF is still challenging due to the risk of life-threatening ventricular arrhythmias caused by non-selective antiarrhythmic drugs. Therefore, the search for safer and more selective anti-AF medications is ongoing. In this study, we summarized phytochemicals with atrial-selective properties as potential candidates for AF drug discovery. EVIDENCE ACQUISITION: PubMed, Embase, Web of Science, and Scopus were searched using relevant keywords, ultimately identifying sixteen phytochemicals with demonstrated effects on atrial-selective anti-AF targets. RESULTS: Across the included studies, phytochemicals were reported to modulate several atrial-selective ion channels, including voltage-gated K CONCLUSION: The findings of this study highlight several promising molecular targets for atrial-selective anti-AF drug development. Among these, acacetin and resveratrol derivatives show notable potential due to their ability to modulate multiple atrial-selective ion channels, supporting their further evaluation as lead compounds. GRAPHICAL ABSTRACT: Image: see text Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of mortality and life-threatening complications, including myocardial infarction, heart failure, and stroke. Although antiarrhythmic drugs (AADs) are the cornerstone of AF treatment, their ventricular proarrhythmic side effects, which are a result of their non-selective mechanism of action, have limited their efficacy. This review aims to identify phytochemicals with atrial-selective anti-AF characteristics that have demonstrated efficacy and selectivity in clinical or preclinical studies and introduces potential plant derivatives that could be regarded as promising candidates for future research into AF drug discovery. Voltage-gated Na