Zhao Zhenying, Yin Yongqiang, Wu Hong, Jiang Min, Lou Jianshi, Bai Gang, Luo Guo'an
College of Pharmacy, Nankai University, Tianjin, P.R. China.
Cell Physiol Biochem. 2013;32(5):1342-53. doi: 10.1159/000354532. Epub 2013 Nov 22.
BACKGROUND/AIMS: Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms.
A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by.
Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine.
Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect.
背景/目的：牛蒡子苷元具有生物活性，但其在细胞和离子通道水平的潜在机制尚未完全明确。因此，本研究旨在确定牛蒡子苷元在体内的抗心律失常作用及其细胞靶点和机制。
通过持续输注乌头碱建立大鼠心律失常模型，记录室性早搏、室性心动过速和死亡的发作时间。采用膜片钳记录技术，测量并分析正常大鼠心肌细胞和乌头碱诱导的心律失常大鼠心肌细胞的动作电位时程（APD）、钠电流（I(Na)）、L型钙电流（I(Ca,L)）和瞬时外向钾电流（I(to)）。
牛蒡子苷元显著延迟了乌头碱诱导的大鼠模型中心律失常的发作。100 μM牛蒡子苷元可缩短50%和90%复极化（APD50和APD90）；该剂量的牛蒡子苷元还可抑制1 μM乌头碱引起的APD50和APD90延长。牛蒡子苷元抑制I(Na)和I(Ca,L)，并通过加速激活过程和延迟失活过程减弱乌头碱增加的I(Na)和I(Ca,L)。牛蒡子苷元通过促进激活过程和延迟失活过程增强Ito，并恢复乌头碱诱导降低的Ito。
牛蒡子苷元在体内和体外均显示出抗心律失常作用。在电生理学背景下，I(Na)、I(Ca,L)和I(to)可能是牛蒡子苷元的多个靶点，从而导致其抗心律失常作用。
