Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou, 225000, Jiangsu, China.
Jiangsu Key Laboratory of Animal Infectious Diseases and Zoonosis Prevention and Control, Yangzhou, 225001, China.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1579-1588. doi: 10.1007/s00210-021-02076-4. Epub 2021 Mar 19.
Aloperine (ALO), a quinolizidine alkaloid extracted from Sophora alopecuroides L., modulates hypertension, ventricular remodeling, and myocardial ischemia. However, few studies have evaluated the effects of ALO on other cardiovascular parameters. Accordingly, in this study, we used a rat model of aconitine-induced ventricular arrhythmia to assess the effects of ALO. Notably, ALO pretreatment delayed the onset of ventricular premature and ventricular tachycardia and reduced the incidence of fatal ventricular fibrillation. Moreover, whole-cell patch-clamp assays in rats' ventricular myocyte showed that ALO (3, 10, and 30 μM) significantly reduced the peak sodium current density of voltage-gated Na channel currents (I) in a concentration-dependent manner. The gating kinetics characteristics showed that the steady-state activation and recovery curve were shifted in positive direction along the voltage axis, respectively, and the steady-state inactivation curve was shifted in negative direction along the voltage axis, i.e., which was similar to the inhibitory effects of amiodarone. These results indicated that ALO had anti-arrhythmic effects, partly attributed to I inhibition. ALO may act as a class I sodium channel anti-arrhythmia agent.
槐定碱（ALO）是从苦参中提取的一种喹诺里西啶生物碱，可调节高血压、心室重构和心肌缺血。然而，很少有研究评估 ALO 对其他心血管参数的影响。因此，在这项研究中，我们使用乌头碱诱导的大鼠室性心律失常模型来评估 ALO 的作用。值得注意的是，ALO 预处理可延迟室性期前收缩和室性心动过速的发作，并降低致命性室颤的发生率。此外，大鼠心室肌细胞的全细胞膜片钳实验表明，ALO（3、10 和 30 μM）可显著降低电压门控钠通道电流（I）的峰值钠电流密度，呈浓度依赖性。门控动力学特征表明，稳态激活和恢复曲线分别沿电压轴正向移动，稳态失活曲线沿电压轴负向移动，这与胺碘酮的抑制作用相似。这些结果表明，ALO 具有抗心律失常作用，部分归因于 I 抑制。ALO 可能作为一种 I 类钠通道抗心律失常药物。
