Erianin alleviates doxorubicin-induced cardiotoxicity by activating the Keap1-Nrf2 signaling pathway

Doxorubicin (DOX) has significant toxic side effects on cardiomyocytes, and existing preventive drug dexrazoxane has serious side effects. Therefore, in-depth research on drugs that can enhance the antitumor effect of DOX and simultaneously reduce its cardiotoxicity is of crucial significance. Our study explored the regulatory role of Erianin in DOX-induced cardiotoxicity and the specific molecular mechanism.

In this study, we constructed a myocardial injury model in mice with DOX. The toxic side effects of DOX on the organism were determined by recording the weight changes of the mice and calculating the spleen index and heart-tibia ratio of the mice. The degree of myocardial injury in mice was evaluated by methods such as echocardiography and Sirius red staining. Further in vivo experiments were conducted to verify whether the silencing of Nrf2 could block the protective effect of Erianin on myocardial cells.

We found Erianin significantly alleviated DOX-induced cardiomyocyte injury (p < 0.0001), increased heart tissue pumping efficiency and contractility (p < 0.001), and reduced myocardial cell fibrosis. Mechanism study showed that Erianin can bind to Keap1, promote its ubiquitination and autophagic degradation, increase the acetylation of lysine 599 site in Nrf2 protein, and activate the antioxidant stress response.

Taken together, our study had for the first time elucidated the molecular mechanism by which Erianin alleviated DOX-induced myocardial injury by activating the Keap1-Nrf2 signaling pathway. It provides a theoretical basis for the development of Erianin as a potential protective drug for DOX-induced cardiotoxicity. It has very important clinical application and translational value.