Mechanism of Ferroptosis in Cardiovascular Disease and Its Regulation by Natural Compounds: A Narrative Review

Abstract

Abstract Cardiovascular disease (CVD) continues to be a worldwide health issue characterized by rising rates of illness and death. Ferroptosis is a form of iron-dependent regulated cell death defined by lipid peroxidation and glutathione depletion, and it has been progressively associated with the development of cardiovascular disease. This narrative review is based on 54 articles that have systematically explored the mechanisms of ferroptosis in the setting of CVDs such as myocardial ischemia-reperfusion injury, doxorubicin-induced cardiotoxicity, myocardial infarction, and atherosclerosis during the last five years. We emphasize the significance of 35 natural compounds and 19 Traditional Chinese Medicine formulations in regulating ferroptosis via important pathways including the Nrf2/HO-1 pathway, GPX4, and iron metabolism regulation. We observe promising preclinical efficacy in this area, but clinical translation is hampered by low bioavailability and undefined molecular targets. Future strategies such as nanoparticle delivery systems and omics-based approaches could help bridge this gap.