Abstract
Xin Su Ning (XSN) is a patented multicomponent medicine, which was certified in 2005 by the China State Food and Drug Administration to be produced pharmaceutically and to be used clinically. The XSN capsule was developed from an effective formula composed by Prof. Shuwen Ding of Shandong University of Traditional Chinese Medicine. Through more than 30 years of clinical observation, Prof. Ding concluded that XSN has a significant effect on arrhythmia with phlegm-heat heart-disturbed syndrome according to the traditional Chinese medicine (TCM) diagnosis. XSN, derived from a classical TCM formula Huanglian Wen Dan Decoction, is formulated with 11 Chinese herbal medicines to treat cardiac ventricular arrhythmia. Clinical evidence suggests that it is particularly efficacious for the arrhythmias induced by cardiac ischemia and viral myocarditis without obvious adverse reactions being reported. Cellular electrophysiological studies in ventricular myocytes revealed that XSN prolongs the duration and suppresses the amplitude of the action potential (AP), which is supported by the blockage of sodium and potassium channels indicating the characteristics of class I and III antiarrhythmic drugs. A recently reported double-blind, placebo-controlled, multicenter clinical trial of XSN enrolled 861 patients (ChiCTR-TRC-14004180) and showed that XSN significantly inhibited premature ventricular contraction (PVC). The cellular electrophysiological discoveries provided the mechanistic evidence for the clinical efficacy on inhibition of PVC by XSN as demonstrated in the clinical trial. These studies, for the first time, provided exclusive evidence that multicomponent TCM antiarrhythmic medicine can be evaluated using conventional research methods that have been used for antiarrhythmic drug discoveries for decades. We aimed to give a comprehensive review on XSN including its origin with the support of TCM theory, its pre-licensing clinical use and development, and its pharmacological and clinical study discoveries. The review will be summarized with the discoveries reported in a novel network pharmacological study that introduced a weight coefficient, which made it possible to evaluate the pharmacological properties of the TCM formula with regard to its formation based on TCM theory. Limitations regarding XSN’s basic and clinical research and possible future studies are listed. We hope that the advances in how XSN was studied may offer useful guidance on how other TCM could be studied with respect to the integrity of the TCM formulas.
Highlights
Chinese medicine has been practiced and developed for thousands of years along with the Chinese civilization
We aim to present a comprehensive review of Xin Su Ning (XSN) that would answer the following questions: 1) The development history of XSN as an antiarrhythmic traditional Chinese medicine (TCM) 2) What are the pharmacological properties of XSN as a multicomponent antiarrhythmic medicine? 3) Why does XSN have to be multi-herbal and formulated with the 11 particular herbs? 4) What are the TCM theories that guide the formation of the XSN formula? 5) What are the pharmacological properties of the individual herbs that formulated XSN? 6) What are the pharmacological properties of some of the compounds isolated from these herbs? 7) Why does XSN not display proarrhythmic reactions while effectively treating cardiac arrythmias? 8) The limitation of the available basic and clinical studies of XSN and possible further studies
XSN as a clinically effective antiarrhythmic TCM displays the characteristics of class I and III antiarrhythmics, which was confirmed using conventional cellular electrophysiological research methods that have been used for discovering antiarrhythmic drugs for the last few decades
Summary
Chinese medicine has been practiced and developed for thousands of years along with the Chinese civilization. It is one of the welldeveloped traditional medicines in the world with comprehensive theories to guide the everyday practices; traditional Chinese medicine (TCM) accumulated rich medical knowledge in treating patients with sufficient efficacies. Arrhythmia can be caused by many cardiovascular diseases such as coronary heart disease, rheumatic heart disease, hypertensive heart disease, and viral myocarditis, and it can be caused by the side effects of drugs. Treating arrhythmia with currently prescribed drugs or radiofrequency ablation all have limitations, in elderly patients, who have increased risks of hypertension, diabetes mellitus, and coronary heart diseases. Many antiarrhythmic drugs may inhibit certain cardiac functions and cause further arrhythmia, or the proarrhythmic effect, as side effects, which limits the clinical use of existing drug treatments due to poor tolerance and compliance (Huang and Wang, 2004; Li, 2011)
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