Natural Compounds From Traditional Chinese Medicine Against Doxorubicin‐Induced Cardiotoxicity: Biological Mechanisms and Therapeutic Potential

The clinical application of doxorubicin (DOX) is severely restricted by its dose-dependent cardiotoxicity. This study aimed to investigate the protective mechanisms of traditional Chinese medicine-derived natural compounds (TCM-NCs) against DOX-induced cardiotoxicity. A systematic analysis was performed on 104 preclinical studies (encompassing in vivo and in vitro models) retrieved from PubMed, Web of Science and Embase, summarising the cardioprotective effects and mechanisms of 65 TCM-NCs. These compounds exert multitarget protective effects by modulating six core pathways: oxidative stress/ferroptosis, apoptosis, inflammation/pyroptosis, mitochondrial homeostasis, autophagy and endoplasmic reticulum stress. Target validation further identified Nrf2, Sirt1, mTOR and AMPK as potential central hub nodes underlying their protective actions. These findings offer a theoretical foundation and promising drug candidates for the prevention of chemotherapy-related cardiac injury, with future research directions focusing on clinical translation and druggability optimisation.