Arctigenin, a Potential Anti-Arrhythmic Agent, Inhibits Aconitine-Induced Arrhythmia by Regulating Multi-Ion Channels

Abstract

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. Methods: 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. Results: 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 I_to by facilitating the activation process and delaying the inactivation process, and recoverd the decreased I_to induced by aconitine. Conclusions: 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.