Andrographolide inhibits arrhythmias and is cardioprotective in rabbits

// Mengliu Zeng 1, * , Wanzhen Jiang 1, * , Youjia Tian 1 , Jie Hao 1 , Zhenzhen Cao 1 , Zhipei Liu 1 , Chen Fu 1 , Peihua Zhang 1 and Jihua Ma 1 1 Cardio-Electrophysiological Research Laboratory, Medical College of Wuhan University of Science and Technology, Wuhan, Hubei, China * These authors have contributed equally to this work Correspondence to: Jihua Ma, email: mjhua@wust.edu.cn Keywords: andrographolide, sodium current, L-type calcium current, action potential, arrhythmia Received: January 17, 2017      Accepted: April 21, 2017      Published: May 22, 2017 ABSTRACT Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na + (I Na ), Ca 2+ (I CaL ), and K + (I K1 , I Kr , I to and I Kur ) currents were recorded using whole-cell patch clamp and current clamp techniques. Additionally, the effects of andrographolide on aconitine-induced arrhythmias were assessed on electrocardiograms in vivo . We found that andrographolide shortened action potential duration and reduced maximum upstroke velocity in rabbit left ventricular and left atrial myocytes. Andrographolide attenuated rate-dependence of action potential duration, and reduced or abolished delayed afterdepolarizations and triggered activities induced by isoproterenol (1 μM) and high calcium ([Ca 2+ ] o =3.6 mM) in left ventricular myocytes. Andrographolide also concentration-dependently inhibited I Na and I CaL , but had no effect on I to , I Kur , I K1 , or I Kr in rabbit left ventricular and left atrial myocytes. Andrographolide treatment increased the time and dosage thresholds of aconitine-induced arrhythmias, and reduced arrhythmia incidence and mortality in rabbits. Our results indicate that andrographolide inhibits cellular arrhythmias (delayed afterdepolarizations and triggered activities) and aconitine-induced arrhythmias in vivo , and these effects result from I Na and I CaL inhibition. Andrographolide may be useful as a class I and IV antiarrhythmic therapeutic.