Investigation of the Cellular Pharmacological Mechanism and Clinical Evidence of the Multi-Herbal Antiarrhythmic Chinese Medicine Xin Su Ning
Investigation of the Cellular Pharmacological Mechanism and Clinical Evidence of the Multi-Herbal Antiarrhythmic Chinese Medicine Xin Su Ning
复制标题
复方抗心律失常中药心苏宁的细胞药理机制及临床证据研究
DOI：
10.3389/fphar.2020.00600
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发表时间：
2020-04
影响因子：
5.6
通讯作者：
Ca
中科院分区：
文献类型：
--
作者：
Ma Yu-ling;Hu Rou-Mu;Yang Xinchun;Wang Taiyi;Noble Penelope J.;Wilkins Robert;Ellory Clive;Carr Carolyn;Noble Denis;Yang Jiefu;Lu Weixing;Zhang Junhua;Hu Hongde;Guo Xiaomei;Chen Min;Wu Yang;Wei Meng;Mao Jingyuan;Ma Xiaochang;Qin Ling;Wu Huanlin;Lu Feng;Ca
心苏宁（XSN）是一种中国专利和认证的多草药，自2005年以来已在中国上市，用于治疗室性心律失常，包括缺血性心脏病和病毒性心肌炎引起的心律失常，未见不良反应报告。因此，研究XSN作为一种多组分药物如何发挥其临床疗效，以及XSN的治疗效果是否可以通过标准的临床试验研究来验证，是至关重要的。在本文中，我们报告了我们在细胞电生理学研究和一项三臂、随机、双盲、安慰剂对照、平行组、多中心试验中的发现。采用常规电生理技术研究XSN的抗肿瘤作用机制。然后用心室肌细胞的人类动作电位（AP）的计算机模拟对数据进行建模。该临床试验共有861名合格的参与者以2：2：1的比例随机分配接受XSN，美西律或安慰剂4周。主要和次要终点分别为室性早搏（PVC）计数和PVC相关症状的变化。本试验已在中国临床试验注册中心注册（ChiCTR-TRC-14004180）。我们发现XSN以剂量依赖性、可逆的方式延长心室肌细胞的AP时程，并阻断钾通道。XSN组减少PVC的总有效率为65.85%，安慰剂组为27.27%，两组比较有显著性差异（P < 0.0001）。未观察到可归因于XSN的严重不良反应。总之，XSN是一种治疗PVC的有效多组分抗心律失常药物，对患者无不良影响，我们早期出版物中报告的其I类和III类药理学抗心律失常机制（阻断hERG钾通道和hNaV 1.5钠通道）以及本报告中提供的心室肌细胞中的HAP持续时间和人类AP的计算机模拟令人信服地支持了这一点。
Xin Su Ning (XSN), a China patented and certified multi-herbal medicine, has been available in China since 2005 for treating cardiac ventricular arrhythmia including arrhythmia induced by ischemic heart diseases and viral myocarditis, without adverse reactions being reported. It is vitally important to discover pharmacologically how XSN as a multicomponent medicine exerts its clinical efficacy, and whether the therapeutic effect of XSN can be verified by standard clinical trial studies. In this paper we report our discoveries in a cellular electrophysiological study and in a three-armed, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Conventional electrophysiological techniques were used to study the cellular antiarrhythmic mechanism of XSN. Data was then modeled with computational simulation of human action potential (AP) of the cardiac ventricular myocytes. The clinical trial was conducted with a total of 861 eligible participants randomly assigned in a ratio of 2:2:1 to receive XSN, mexiletine, or the placebo for 4 weeks. The primary and secondary endpoint was the change of premature ventricular contraction (PVC) counts and PVC-related symptoms, respectively. This trial was registered in the Chinese Clinical Trial Register Center (ChiCTR-TRC-14004180). We found that XSN prolonged AP duration of the ventricular myocytes in a dose-dependent, reversible manner and blocked potassium channels. Patients in XSN group exhibited significant total effective responses in the reduction of PVCs compared to those in the placebo group (65.85% vs. 27.27%, P < 0.0001). No severe adverse effects attributable to XSN were observed. In conclusion, XSN is an effective multicomponent antiarrhythmic medicine to treat PVC without adverse effect in patients, which is convincingly supported by its class I & III pharmacological antiarrhythmic mechanism of blocking hERG potassium channels and hNaV1.5 sodium channel reported in our earlier publication and prolongs AP duration both in ventricular myocytes and with computational simulation of human AP presented in this report.
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影响因子：
3
作者：
Wendl MC
通讯作者：
Wendl MC
影响因子：
5.5
作者：
P. Kowey;G. Yan
通讯作者：
P. Kowey;G. Yan
影响因子：
37.8
作者：
Marcus, Gregory M.
通讯作者：
Marcus, Gregory M.
影响因子：
158.5
作者：
Frolkis, JP;Pothier, CE;Lauer, MS
通讯作者：
Lauer, MS
DOI：
10.1002/j.1552-4604.1992.tb03797.x
发表时间：
1992-11
期刊：
The Journal of Clinical Pharmacology
影响因子：
--
作者：
E. Williams
通讯作者：
E. Williams