Abstract
Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na+ (INa), Ca2+ (ICaL), and K+ (IK1, IKr, Ito and IKur) 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 ([Ca2+]o=3.6 mM) in left ventricular myocytes. Andrographolide also concentration-dependently inhibited INa and ICaL, but had no effect on Ito, IKur, IK1, or IKr 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 INa and ICaL inhibition. Andrographolide may be useful as a class I and IV antiarrhythmic therapeutic.
Highlights
The traditional medical herb, Andrographis paniculata (Burm.f.) Wall. ex Nees, has been used for centuries to treat a variety of diseases in China
Our results indicate that andrographolide inhibits cellular arrhythmias and aconitine-induced arrhythmias in vivo, and these effects result from INa and ICaL inhibition
This study found that andrographolide inhibited INa and ICaL in left ventricular myocytes (LVMs) and left atrial myocytes (LAMs) in a concentration-dependent manner
Summary
The traditional medical herb, Andrographis paniculata (Burm.f.) Wall. ex Nees, has been used for centuries to treat a variety of diseases in China. Andrographolide, its major bioactive component, has many pharmacological effects, including antitumor [1, 2], anti-inflammatory [1,2,3,4], antiviral [2], anti-hypertension [5], antioxidant [3, 6, 7], antihyperglycaemic [2], hepatoprotective [2, 7], and cardioprotective properties [5,6,7,8,9,10,11]. Because platelet activation is closely linked to coronary heart disease, andrographolide could be used to treat patients with thromboembolic disorders due to its antiplatelet activity [9,10,11]. This study explored the effects of andrographolide on the aforementioned ion channels and action potentials (APs) to determine its antiarrhythmic mechanism of action
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