Wenxin Keli for the Treatment of Arrhythmia-Systems Pharmacology and In Vivo Pharmacological Assessment.

Xiaofeng Li,Gang Tian,Wuxun Du,Fangjun Deng,Hucheng Zhao,Rui Tao,Lili Sun,Jinhong Chen,Liang Xu,Shaoqiang Zhang,Yang Yu,Zidong Cong

doi:10.3389/fphar.2021.704622

Abstract

This study employed a systems pharmacology approach to identify the active compounds and action mechanisms of Wenxin Keli for arrhythmia treatment. Sixty-eight components identified in vivo and in vitro by UPLC/Q-TOF-MS were considered the potential active components of Wenxin Keli. Network pharmacology further revealed 33 key targets and 75 KEGG pathways as possible pathways and targets involved in WK-mediated treatment, with the CaMKII/CNCA1C/Ca2+ pathway being the most significantly affected. This finding was validated using an AC-induced rat arrhythmias model. Pretreatment with Wenxin Keli reduced the malignant arrhythmias and shortened RR, PR, and the QT interval. Wenxin Keli exerted some antiarrhythmic effects by inhibiting p-CaMKII and intracellular Ca2+ transients and overexpressing CNCA1C. Thus, suppressing SR Ca2+ release and maintaining intracellular Ca2+ balance may be the primary mechanism of Wenxin Keli against arrhythmia. In view of the significance of CaMKII and NCX identified in this experiment, we suggest that CaMKII and NCX are essential targets for treating arrhythmias.

Highlights

Arrhythmias are a group of conditions that cause the heart to beat irregularly (O’Rourke et al, 2016)
The five herbs had significant target overlap among them despite the differences in the number of each herb-related target. These results suggested that the different herbal drugs contained in Wenxin Keli (WK) possibly worked synergistically in regulating similar targets
4) New antiarrhythmic strategy: This study demonstrated that WK had therapeutic effects in AC-induced rat arrhythmias by inhibiting p-calmodulin-dependent protein kinaseII (CaMKII), over-expressing CNCA1C, and inhibiting intracellular Ca2+ transients

Summary

Introduction

Arrhythmias are a group of conditions that cause the heart to beat irregularly (O’Rourke et al, 2016). It may remain asymptomatic or lead to other cardiovascular disorders, heart failure, stroke, and cardiac arrest. Severe arrhythmias, such as ventricular arrhythmias, have limited treatment options, causing them to be fatal (Hong et al, 2019). Numerous ongoing studies have reported treatment solutions for arrhythmias (Tian et al, 2019). Effective pharmaceutical agents with fewer side effects are being explored.

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Discussion

Conclusion