Biology (Basel). 2026 May 23;15(11):824. doi: 10.3390/biology15110824.
ABSTRACT
Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation, playing a critical role in the pathogenesis of various cardiomyopathies, including hypertrophic, dilated, diabetic, ischemic, doxorubicin-induced, and septic cardiomyopathy, as well as myocardial ischemia-reperfusion injury. This article provides a comprehensive narrative review of the molecular mechanisms of ferroptosis-centered on dysregulation of the GPX4/System Xc- axis, iron metabolism, and lipid metabolism-and its role in cardiovascular diseases, with a specific focus on the cardioprotective effects of Traditional Chinese Medicine (TCM). Through a systematic analysis of recent literature, we highlight active components (e.g., baicalin, ginsenoside Rg3, resveratrol, tanshinone IIA), compound formulations (e.g., Qishen Granule, Zhilong Huoxue Tongyu Capsule), and electroacupuncture therapy, which exert effects via multi-target regulation of ferroptosis-related pathways such as Nrf2/HO-1/GPX4, p53/SLC7A11, and PI3K/AKT. Evidence indicates that TCM interventions effectively alleviate cardiomyocyte ferroptosis by activating the Nrf2 antioxidant pathway to upregulate GPX4/SLC7A11, modulating iron metabolism to reduce labile iron pools, and inhibiting ACSL4/ALOX15-mediated lipid peroxidation, with these effects validated in diverse cardiovascular disease models showing improved cardiac function. Targeting ferroptosis offers a novel therapeutic strategy for cardiovascular diseases, and TCM-with its synergistic multi-component, multi-target, multi-pathway advantages-holds significant potential in this context. Future research should prioritize elucidating complex network mechanisms and advancing clinical translation via high-quality studies to provide new theoretical foundations and drug candidates for cardiovascular disease management.
PMID:42274475 | DOI:10.3390/biology15110824