Eupatilin attenuates doxorubicin-induced cardiotoxicity by activating the PI3K-AKT signaling pathway in mice.

Eupatilin is a pharmacologically active flavonoid with a variety of biological activities, such as anticancer, anti-inflammatory, antioxidant, neuroprotective, anti-allergic and cardioprotective effects. However, whether eupatilin has protective effects on doxorubicin-induced cardiotoxicity remains unknown. Thus, this study aimed to investigate the role of eupatilin in doxorubicin-induced cardiotoxicity. Mice were exposed to a single dose of doxorubicin (15 mg/kg) to generate doxorubicin-induced cardiotoxicity or normal saline as a control. To explore the protective effects, mice were intraperitoneally injected with eupatilin daily for 7 days. Then, we examined the changes in cardiac function, inflammation, apoptosis, and oxidative stress to evaluate the effects of eupatilin on doxorubicin-induced cardiotoxicity. Additionally, RNA-seq analysis was introduced to explore the potential molecular mechanisms. Eupatilin ameliorated doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and cardiomyocyte apoptosis and ameliorated doxorubicin-induced cardiac dysfunction. Mechanistically, eupatilin activated the PI3K-AKT signaling pathway, as evidenced by RNA-seq analysis and Western blot analysis. This study provides the first evidence that eupatilin ameliorates doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and apoptosis. Pharmacotherapy with eupatilin provides a novel therapeutic regimen for doxorubicin-induced cardiotoxicity.