Key result
Herbacetin mitigated doxorubicin-induced myocardial damage and cardiac dysfunction in vivo and in vitro by inhibiting oxidative stress and lipid peroxidation via direct binding to ACSL4.
Why the study?
Dexrazoxane is the only FDA-approved drug for doxorubicin-induced cardiotoxicity but may diminish cancer cell sensitivity to chemotherapy, leaving an urgent need for safe and effective therapeutic alternatives.
Does herbacetin mitigate doxorubicin-induced cardiotoxicity in preclinical models?
Does herbacetin mitigate doxorubicin-induced cardiotoxicity in preclinical models?
Herbacetin shows therapeutic potential in mitigating doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and ferroptosis via ACSL4 modulation in preclinical models.
Herbacetin warrants preclinical follow-up for DOX cardiotoxicity; leaves open clinical translation pending human efficacy and safety trials.
The chemotherapy agent doxorubicin (DOX) is significantly constrained in its clinical application due to its notable cardiotoxicity. Dexrazoxane is the only drug approved by the FDA for the prevention of DOX-induced carditoxicity; however, it may also diminish the sensitivity of cancer cells to DOX chemotherapy. Consequently, there is an urgent need for the development of safe and effective therapeutic agents to mitigate the cardiotoxic effects induced by DOX. In this study, C57BL/6J mice and H9C2 cardiomyocytes were employed to establish models of DOX-induced cardiotoxicity. We examined the effects of herbacetin on myocardial damage, cardiac function, oxidative stress, ferroptosis and the associated signaling pathways using a variety of experimental techniques. Our results demonstrated that herbacetin mitigated DOX-induced myocardial damage and cardiac dysfunction both in vivo and in vitro. Mechanistically, herbacetin inhibits oxidative stress and lipid peroxidation by directly binding to tyrosine 342 of acyl-CoA synthetase long-chain family member 4 (ACSL4). This interaction inhibits lipid peroxidation and ferroptosis, suggesting that herbacetin may serve as a promising ferroptosis inhibitor and therapeutic agent for diseases associated with ferroptosis. This study underscores the therapeutic potential of herbacetin in DOX-induced cardiotoxicity and highlights the importance of modulating ACSL4 activity and inhibiting lipid peroxidation in diseases associated with ferroptosis.
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Yang et al. (2025) studied Doxorubicin-induced cardiotoxicity. Herbacetin was evaluated on Myocardial damage, cardiac function, oxidative stress, and ferroptosis. Herbacetin mitigated doxorubicin-induced myocardial damage and cardiac dysfunction in vivo and in vitro by inhibiting oxidative stress and lipid peroxidation via direct binding to ACSL4.
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