Monotropein attenuates doxorubicin-induced oxidative stress, inflammation, and arrhythmia via the AKT signal pathway.

As a glycoside iridoid, monotropein (MON) has a wide range of pharmacological properties, including anti-inflammatory, antioxidant, and anti-apoptotic effects. However, few studies have investigated MON's cardiovascular protective effects. Therefore, this study aimed to explore the role of MON in doxorubicin (DOX)-induced cardiotoxicity. To establish the myocardial toxicity model, mice were intraperitoneally injected with DOX. After admimistration of DOX, myocardial injury markers were increased, cardiac function was reduced, and pathological changes were observed in the myocardium, indicating successful construction of the myocardial injury model. Our study showed that MON treatment mitigated DOX-induced myocardial damage and improved cardiac dysfunction. In addition, DOX-treated mice displayed higher levels of inflammation and oxidative stress, while MON treatment also reversed these pathological changes. Moreover, DOX-treated mice were more susceptible to ventricular fibrillation, whereas MON reduced ventricular fibrillation incidence. Further studies have shown that MON could reverse DOX-induced inhibition of the AKT signaling pathway. Besides, the application of AKT inhibitor could partially abolish MON's cardioprotective effects. To conclude, this study demonstrated the ability of MON to reduce DOX-induced myocardial damage, cardiac dysfunction, inflammation, and oxidative stress, as well as ventricular fibrillation risk. These may attributable to the activation of the AKT pathway.