Traditional Chinese Medicine YangxinDingji alleviates arrhythmias through inhibition of sodium and L-type calcium channels.

Ethnopharmacological Relevance: The Chinese herbal formula YangxinDingji (YXDJ), derived from the classic ancient formula Zhigancao decoction that originated from Zhang Zhongjing's "shang han lun", is a modern preparation of a classic prescription, and is used for arrhythmia treatment in China. However, its antiarrhythmic mechanisms are not fully elucidated.

Aim Of The Study: This study aimed to investigate the pharmacological and molecular mechanisms of YXDJ.

Materials And Methods: Antiarrhythmic effects were evaluated in isolated guinea pig hearts subjected to ischemia/reperfusion (I/R) or isoproterenol (ISO) challenge, and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) utilizing a multi-electrode array (MEA). Patch clamp recordings assessed the effects of YXDJ on sodium (I, I) and L-type calcium (I) currents, while potassium currents (I, I) were studied in heterologous cells. Optical mapping observed electrical activities and calcium transients.

Results: YXDJ pretreatment at concentrations of 0.25, 0.5, and 1.0 mg/ml effectively prevented ventricular arrhythmias induced by I/R or ISO challenge, and mitigated electrical stimulation-induced arrhythmias in hiPSC-CMs. YXDJ inhibited I, I, and I currents in a concentration-dependent manner without affecting I and I, inhibited abnormal electrical activities and excitation reentry, decreased action potential duration dispersion and heterogeneity of excitation conduction, and restored intracellular calcium homeostasis.

Conclusions: Our results demonstrate that YXDJ exerts its antiarrhythmic effect through the inhibition of inward depolarizing currents, which prevents alterations in left ventricular repolarization dispersion. This leads to synchronized repolarization and a reduction in excitation reentry. Collectively, these findings suggest that YXDJ is a promising candidate for the treatment of arrhythmias.