Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels

Barbaloin (10-beta-D-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)-anthracenone) is extracted from the aloe plant and has been reported to have anti-inflammatory, antitumor, antibacterial, and other biological activities. Here, we investigated the effects of barbaloin on cardiac electrophysiology, which has not been reported thus far. Cardiac action potentials (APs) and ionic currents were recorded in isolated rabbit ventricular myocytes using whole-cell patch-clamp technique. Additionally, the antiarrhythmic effect of barbaloin was examined in Langendorff-perfused rabbit hearts. In current-clamp recording, application of barbaloin (100 and 200 mu mol/L) dose-dependently reduced the action potential duration (APD) and the maximum depolarization velocity (Vmax), and attenuated APD reverse-rate dependence (RRD) in ventricular myocytes. Furthermore, barbaloin (100 and 200 mu mol/L) effectively eliminated ATX II-induced early afterdepolarizations (EADs) and Ca2+-induced delayed afterdepolarizations (DADs) in ventricular myocytes. In voltageclamp recording, barbaloin (10-200 mu mol/L) dose-dependently inhibited L-type calcium current (I-Ca.L) and peak sodium current (I-Na.P) with IC50 values of 137.06 and 559.80 mu mol/L, respectively. Application of barbaloin (100, 200 mu mol/L) decreased ATX II-enhanced late sodium current (I-Na.L) by 36.6%+/- 3.3% and 71.8%+/- 6.5%, respectively. However, barbaloin up to 800 mu mol/L did not affect the inward rectifier potassium current (I-K1) or the rapidly activated delayed rectifier potassium current (I-Kr) in ventricular myocytes. In Langendorff-perfused rabbit hearts, barbaloin (200 mu mol/L) significantly inhibited aconitine-induced ventricular arrhythmias. These results demonstrate that barbaloin has potential as an antiarrhythmic drug.