PAE ameliorates doxorubicin-induced cardiotoxicity via suppressing NHE1 phosphorylation and stimulating PI3K/AKT phosphorylation

Doxorubicin (DOX), a broad-spectrum anti-tumor drug, has severe cardiotoxic side effects that limit its clinical application. Perillaldehyde (PAE) is the main component of volatile oil extracted from the stems and leaves of Herbaceous plant-perilla, which demonstrates antioxidant, anti-inflammatory, hypolipidemic, and other health functions. The present study aimed to explore the protective effect of perillaldehyde on DOX-induced car-diotoxicity in rats and to confirm its possible mechanism. The results showed that PAE could significantly improve cardiac function, alleviate myocardial fibrosis, and attenuate oxidative stress and inflammatory re-sponses in DOX-induced cardiotoxicity in rats. Mechanistically, PAE could DOX-induced cardiotoxicity, which is related to its regulation of the PI3K/Akt signaling pathway and inhibition of NHE1 phosphorylation. Therefore, the finding demonstrates that perillaldehyde may be a promising cardioprotective agent for the prevention and treatment of cardiotoxicity caused by DOX.