Shenlian-Fumai formula attenuates ventricular arrhythmias via modulating sodium channel function in heart failure mice

ABSTRACT Ethnopharmacological relevance Shenlian-Fumai Formula (SLFM) is a traditional Chinese medicine (TCM) prescription that originates from the classical formulas Gui Pi Tang and Huanglian Wendan Tang. It has been further developed within the TCM Qi-Blood theory for the management of palpitations and related cardiac symptoms. Clinical trials have evaluated SLFM in patients with ventricular arrhythmias (VAs) associated with heart failure (HF). Aim of the study To evaluate the cardioprotective and antiarrhythmic effects of SLFM in a mouse model of HF with VAs and to explore its underlying mechanisms with a focus on sodium channel regulation. Materials and methods HF was induced in male C57BL/6J mice by transverse aortic constriction (TAC). Mice were randomly divided into six groups: Control, HF model (Model), SLFM low-dose (SLFM-L, 4.66 g/kg/d), SLFM medium-dose (SLFM-M, 9.31 g/kg/d), SLFM high-dose (SLFM-H, 18.62 g/kg/d), and Mexiletine (0.32 g/kg/d) groups. Cardiac function was evaluated by echocardiography, serum BNP, heart and lung weight indices, and myocardial histology were also assessed. Electrocardiographic (ECG) parameters and VA occurrence were recorded at baseline and after isoproterenol injection. Patch-clamp was used to assess action potentials (APs) and sodium currents (I Na ) in isolated cardiomyocytes. The role of CaMKII was examined using KN93. qPCR detected expression levels of CaMKII and SCN5A. Results SLFM dose-dependently improved cardiac function, reduced BNP, alleviated myocardial fibrosis, and lowered VA incidence. It also restored action-potential duration (APD), increased I Na density, and normalized channel kinetics. These effects were partially associated with modulation of CaMKII and SCN5A mRNA expression. Conclusion SLFM exhibits antiarrhythmic and cardioprotective effects in HF by regulating sodium channel function and CaMKII signaling, highlighting its potential as a therapeutic option for HF-related VAs. However, all data were obtained from a single batch of SLFM, limiting generalizability and requiring validation with additional batches and harvest years.