Mechanistic Effects and Complications of Berberine on Cardiac Arrhythmias: A Systematic Review

Background: Arrhythmia is an abnormal sinus rhythm of the heartbeat, and in addition to threatening the patient's health, it may also cause fatal complications. Objectives: The present review study was investigated the effects of berberine (BBR) on cardiac arrhythmias and its possible complications. Methods: A systematic search was conducted on electronic databases such as PubMed/MEDLINE, Web of Science, Scopus, Embase, and Cochrane Library to identify relevant studies published before June 10, 2024. Inclusion criteria were defined based on the study's aim. Two reviewers performed data extraction independently to ensure accuracy and minimize bias. The data were finally extracted and analyzed. Results: Finally, 22 studies were included. BBR revealed antiarrhythmic effects through antioxidant, anti-inflammatory, and anti-apoptotic activity and improved mitochondrial function. Moreover, BBR modulated ion channels and improved electrical remodeling trough inhibited Potassium current (IK), IK1, IKr, IKs, ICa, INa, KATP channels and human ether-a-go-go related gene (hERG) and improved expression of inwardly rectifying potassium (Kir)6.2 and Kir2.1. It also increased action potential duration (APD), prolonged the effective refractory period (ERP), and reduced the frequency and complexity of ventricular premature complexes (VPC). However, it causes some cardiovascular side effects, including prolonged QT interval, bradycardia, and hypotensive effects. BBR may also lead to gastrointestinal complications, immunosuppressive effects, and interaction with concomitant drugs. Conclusion: Although BBR's cardioprotective properties have satisfactory effects on cardiac arrhythmia, it causes prolonged QT interval, bradycardia, hypotension, and cardiotoxicity. However, more clinical studies are needed to obtain more reliable results.