1. Investigation of the Antiarrhythmic Mechanism of the Multi-herbal Medicine Xin Su Ning
Yu-ling Ma1, Robert Wilkins1, Clive Ellory1, Richard Vaughan-Jones1
Mao Peng,2, Zhao Zheng-Sheng2, Xiao-Xiao Zhang2 and Jian-Dong Jiang2
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford UK1
Shaanxi Momentum Pharmaceutical Co., Shaanxi China2
INTRODUCTION
Xing Su Ning (XSN) is a multi-herbal Chinese medicine produced by Momentum Pharmaceutical Co. Ltd. in China, which is sold in China since 2005 for treating cardiac ventricular arrhythmia, especially arrhythmias induced by cardiac ischemia and viral myocarditis (Figure1).
Figure 1:
AIM
To discover the cellular electrophysiological mechanism of the actions of XSN in treating cardiac arrhythmia in patients.
METHODS
Experimental Medicine preparation: Figure 2 outlines the procedure of the extraction of the experimental XSN preparation. It was prepared by ethanol extraction for parts of the herbs and water extraction for the rest of herbs.
Cellular electrophysiology: Ventricular myocytes were isolated from adult rat hearts. The cells were continuously superfused at room temperature with a solution of the following composition (in mM): NaCl, 112; KCl, 5.4; MgC2 1.0; CaCl2 ,1.0; NaH2PO4, 1.0; HEPES, 5.0; Glucose 10; NaHCO2, 24 gassed with 95% O2/5%CO2; pH 7.4. The whole-cell, patch-clamp technique was used to measure action potential as previously described (Ma et al, 2006). . The pipette solution contained (in mM): KCl,140; MgCl2 1.0; EGTA, 5; HEPES, 10; ATP, 2.
XSN was dissolved in the extracellular solution and perfused to the cells.
Figure 2:
Herbal Medicine used in XSN
C Group Herbals
A & B Group herbals
Filtering Procedures &
Discard Solid Parts
Extraction with Water
Mixing Extracts from all the herbs
Extraction with 60% & 70% Ethanol
Heat – dry the Extracts
Powder Form of XSN Preparation
Semi-liquid form of Extracts
Concentrating the Extracts
Figure 3:
RESULTS
Figure 1: The clinical efficacy of Xing Su Ning in comparison with a known antiarrhythmic herbal medicine Xing Lü Ning (XLN)as control. There were 300 patients for XSN and 140 patients for XLN participated the Clinical data collection.
Figure 2: Diagram of the procedure of Xing Su Ning preparation
Figure 3: The effect of XSN on the action potential of cardiac ventricular myocyte. XSN prolong action potential duration in a dose-dependent manner. The left panel shows the superimposed AP at control, XSN 2mg/ml and washout as indicated in the key; the right panel shows the effect of XSN at 4mg/ml.
Figure 4: The reversible effect of XSN on action potential. The effect of XSN on AP duration is plotted against time. AP duration was measured at 90% re-polarization of the action potential.
Figure 5: Concentration-dependent effect of XSN on action potential duration.
XSN at concentration of 1mg/ml has very little effect on action potential duration; at concentrations of 2mg/ml and 4mg/ml, XSN prolong action potential duration significantly (P<0.05).
Figure 4:
CONCLUSION
XSN Prolongs APD, action that increases the effective refractory period which suppress tachyarrhythmias caused by reentry mechanisms. XSN displays the property of Class III antiarrhythmic drugs, such as amiodarone, without adverse reactions. Further studies on the effect of XSN on ionic channels, i.e. potassium channels, will be carried out.
Acknowledgement
The project was sponsored by Momentum Pharmaceutical Co. Ltd. Shaanxi China. We are grateful for the support of the project by Professor Peter Robbins, the Head of the Department of Physiology, Anatomy and Genetics, University of Oxford.
References
Ma, YL., Bates, S. and Gurney, A. (2006). European Journal of Pharmacology. 545:87-92
Figure 5: