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

Frontiers in Pharmacology

Yang Yu¹  Hucheng Zhao¹  Gang Tian²  Wuxun Du³  Zidong Cong³  Shaoqiang Zhang³  Xiaofeng Li³  Jinhong Chen⁴  Rui Tao⁴  Fangjun Deng⁴  Lili Sun⁴  Liang Xu⁶ 

[1] Department of Aeronautics and Astronautics, Tsinghua University, Beijing, China;Department of Cardiology, Teda International Cardiovascular Hospital, Tianjin, China;Department of Cardiology, The Second Affiliated Hospital of Tianjin University of TCM, Tianjin, China;Department of TCM, Tianjin University of TCM, Tianjin, China;School of Pharmacy, Tianjin Medical University, Tianjin, China;Tianjin Medical College, Tianjin, China;

关键词: Wenxin Keli;    arrhythmia;    active compounds;    action mechanisms;    systems phar macology;    Ca2+ balance;   

DOI  :  10.3389/fphar.2021.704622

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown