Yangxin granules alleviate doxorubicin-induced cardiotoxicity by suppressing oxidative stress and apoptosis mediated by AKT/GSK3β/β-catenin signaling

Abstract

Background: Yangxin granules (YXC), a Chinese herbal medicine, have been confirmed to have clinical benefits in the treatment of heart failure. This study examined the effects and molecular mechanisms of YXC in the treatment of doxorubicin-induced cardiotoxicity in vitro. Methods: H9c2 cardiomyocytes were pretreated with YXC (5, 10, or 20 mg/mL) or the AKT inhibitor MK-2206 (50 nM) before doxorubicin treatment (1 µM). Cell apoptosis, viability, inflammatory factor expression (TNF-α, IL-1β, and IL-6), and oxidative stress mediator levels including superoxide dismutase, reactive oxygen species, and malondialdehyde were detected. Results: YXC increased the viability of H9c2 cells. In addition, doxorubicin inhibited AKT/GSK3β/β-catenin signaling, whereas YXC increased the expression of phosphorylated AKT and GSK3β, and β-catenin in doxorubicin-treated H9c2 cells. Moreover, T-cell factor/lymphoid enhancer factor signaling downstream of β-catenin was also activated by YXC. YXC pretreatment also inhibited doxorubicin-induced inflammation, oxidative stress, and apoptosis. However, MK-2206 reversed the effects of YXC in doxorubicin-treated H9c2 cells. Conclusions: YXC alleviates doxorubicin-induced inflammation, oxidative stress, and apoptosis in H9c2 cells. These effects might be mediated by the AKT/GSK3β/β-catenin signaling pathway. YXC might have preventive effects against doxorubicin-induced heart failure.