Andrographolide inhibits arrhythmias and is cardioprotective in rabbits

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.

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches

“…As described in the literature, andrographolide could powerfully ameliorate the progression of atherosclerosis by inhibiting inflammatory reaction, ROS production and foam cell formation, suggesting it can be regarded as a potential therapeutic agent for the prevention and treatment of this pathema (Wu et al, 2018). Besides, in a report with regard to the effect of andrographolide on arrhythmia in rabbits, it was employed as a compound known to be effective at elevating the time and dosage thresholds of aconitine‐induced arrhythmias, as well as decreasing arrhythmia incidence and mortality (Zeng et al, 2017). In conclusion, andrographolide could mediate its cardiovascular protective effect through a variety of molecular biological mechanisms.…”

Mechanism-based targeting of cardiac arrhythmias by phytochemicals and medicinal herbs: A comprehensive review of preclinical and clinical evidence

“…Nees with several cardioprotective effects. Zeng et al ( 21 ) conducted an in vivo experiment with an aconitine-induced arrhythmia animal model as well as in vitro assays, using rabbit left ventricular and left atrial myocytes to confirm their hypothesis that andrographolide has antiarrhythmic effects through modulation of cardiac ion channels. They showed that 20 μM andrographolide suppressed the aconitine-induced arrhythmias in the in vivo rabbit model.…”

Advances on pharmacology and toxicology of aconitine

“…To solve the problem of AC toxicity, medical researchers adopted compatibility and dosage control. Oxymatrine prevented rat arrhythmia through the inhibition of sodium and calcium currents [113]; gallic acid played a remarkably depressant role in INa in rat ventricular myocytes and AC‐induced arrhythmias in vivo [114]; andrographolide treatment increased the time and dosage thresholds of AC‐induced arrhythmias and reduced the incidence and mortality of arrhythmia in rabbits [115]. Zhang et al dynamically observed the dose–toxicity relationship of AC to cardiotoxicity, and the results showed that the dose of AC was closely related to toxicity and pharmacodynamic indexes [116].…”