ORIGINAL RESEARCH published: 06 February 2019 doi: 10.3389/fphar.2019.00070 Edited by: Aiping Lu, Hong Kong Baptist University, Hong Kong Reviewed by: Yu Huang, The Chinese University of Hong Kong, China Lei Chen, Fujian Agriculture and Forestry University, China *Correspondence: Yu-ling Ma yu-ling.ma@dpag.ox.ac.uk Specialty section: This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology Received: 22 August 2018 Accepted: 21 January 2019 Published: 06 February 2019 Citation: Wang T, Xie W, Yu J, Ellory C, Wilkins R, Zhu Y and Ma Y-l (2019) Ion Channel Targeted Mechanisms of Anti-arrhythmic Chinese Herbal Medicine Xin Su Ning. Front. Pharmacol. 10:70. doi: 10.3389/fphar.2019.00070 Ion Channel Targeted Mechanisms of Anti-arrhythmic Chinese Herbal Medicine Xin Su Ning Taiyi Wang 1 , Weiwei Xie 2 , Jiahui Yu 2 , Clive Ellory 1 , Robert Wilkins 1 , Yan Zhu 2 and Yu-ling Ma 1 * 1 Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, 2 Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China Xin Su Ning (XSN) is a China patented and certified herbal medicine used to treat premature ventricular contractions (PVCs) since 2005. A recent completed clinical trial of 861 patients showed that XSN had similar PVC inhibition rate to the class I antiarrhythmic drug mexiletine, at 65.85% for XSN and 63.10% for mexiletine. We have previously reported that XSN prolongs action potential duration (APD) and suppresses action potential amplitude (APA) of the cardiac ventricular myocytes. In this report we aim to reveal the effect of XSN on the ionic channels that govern APD and APA, which would help to explain the cellular electrophysiological mechanism of XSN. Our main findings are: (1) On ECG recorded in isolated rat, in the presence of XSN the amplitude of R wave was significantly decreased and the amplitude of T wave was increased significantly; (2) XSN blocked hNaV1.5 channel stably transfected cell line in a dose-dependent manner with an IC 50 of 0.18 ± 0.02 g/L; and (3) XSN suppresses hERG channels in a dose-dependent manner with an IC 50 of 0.34 ± 0.01 g/L. In conclusion, the clinical antiarrhythmic efficacy of XSN is based on its class I and Class III antiarrhythmic properties by suppression hNaV1.5 channel and hERG channels, which are directly responsible for XSN’s effect on APA suppression and APD prolongation. Keywords: anti-arrhythmic drugs, premature ventricular contractions, Xin Su Ning, Chinese Herbal Medicine, electrophysiology INTRODUCTION Although much research has been carried out in the attempt to gain better understanding of cardiac arrhythmia, and in the search for effective and safe drugs to treat this common cardiac condition, the progress has been not very encouraging due to the multifactor and dynamic nature of the disease’s causes and its development (Rosen, 1988; Weiss et al., 2015). New drug development strategy of targeting ion channels or cellular electrophysiological properties have developed sophistically in the last decades, however the drugs discovered in this scheme are far from satisfactory, due to adverse reactions of the antiarrhythmic drugs (Williams, 1992; Ma et al., 2006; Frommeyer and Eckardt, 2016; O’rourke et al., 2016; Sun et al., 2016). In this report we aimed to study the antiarrhythmic mechanism of a clinically effective multi-herbal/multicomponent Chinese medicine XSN, which we hope to elicit the cellular electrophysiological property of XSN and to provide guidance for clinicians who use XSN to treat cardiac arrhythmia patients, we also hope to open up a research field to understand the antiarrhythmic actions of multicomponent medicine. Frontiers in Pharmacology | www.frontiersin.org 1 February 2019 | Volume 10 | Article 70