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 (INa, INa-L) and L-type calcium (ICa-L) currents, while potassium currents (IKr, IKs) 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 INa, INa-L, and ICa-L currents in a concentration-dependent manner without affecting IKr and IKs, 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.