Ginsenoside Rb1 ameliorates cardiotoxicity triggered by aconitine via inhibiting calcium overload and pyroptosis

Abstract

BackgroundAconitine-induced cardiotoxicity limits the clinical treatment of cardiotonic, cancers and immune-related diseases. Ginsenoside Rb1 (Rb1) is an active ingredient of traditional Chinese medicine with cardioprotective effect. PurposeThis study aims to study the mechanism of aconitine cardiotoxicity and the detoxification mechanism of Rb1.Study Design: MethodsThe regulatory effect of Rb1 on aconitine was evaluated in vitro and in vivo by myocardial enzyme indicators, pathological analysis, CardioECR detection, calcium transient analysis, western blotting and immunohistochemistry. ResultsRb1 (10, 20, 40 mg/kg) alleviated apoptotic myocardial damage caused by aconitine in rats. Furthermore, Rb1 (25, 50, 100 μM) restored the contractile function and field potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by regulating calcium channels and reduced myocardial cell damage by inhibiting the calcium transients of adult rat ventricular myocytes (ARVMs). Rb1 significantly reduced calcium levels in hiPSC-CMs, directly indicating that aconitine-induced calcium overload was alleviated by Rb1. Further, aconitine caused calcium overload by changing the expression of calcium pathway proteins, while Rb1 effectively restored calcium homeostasis. In addition, Rb1 also had a cardioprotective role by inhibiting cell pyroptosis. These results suggested that the maintenance of calcium homeostasis helped to suppress the inflammatory response related to pyroptosis of the heart. ConclusionAconitine-induced cardiotoxicity can be alleviated by Rb1 via restoring calcium homeostasis and inhibiting apoptosis and pyroptosis.