Herbal medicines provide regulation against iron overload in cardiovascular diseases: Informing future applications

Iron is an essential micronutrient for maintaining physiological activities, especially for highly active cardiomyocytes. Inappropriate iron overload or deficiency has a significant impact on the incidence and severity of cardiovascular diseases (CVD). Iron overload exerts potentially deleterious effects on doxorubicin (DOX) cardiomyopathy, atherosclerosis, and myocardial ischemia-reperfusion injury (MI/RI) by participating in lipid peroxides production. Notably, iron overload-associated cell death has been defined as a possible mechanism for ferroptosis. At present, some traditional herbal medicines and extracts have been included in the study of regulating iron overload and the subsequent therapeutic effect on CVD. To give an outline of iron metabolism and ferroptosis in cardiomyocytes and to focus on herbal medicines and extracts to prevent iron overload in CVD. Literature information was systematically collected from ScienceDirect, PubMed, Google Scholar, Web of Science, China National Knowledge Infrastructure, WanFang data, as well as classic books and clinical reports. After understanding the mechanism of iron overload on CVD, this paper reviews the therapeutic function of various herbal medicines in eliminating iron overload in CVD. These include Chinese herbal compound prescriptions (Salvia miltiorrhiza injection, Gegen Qinlian decoction, Tongxinluo, Banxia-Houpu decoction), plant extracts, phenylpropanoids, flavonoids, terpenoids, and polyphenols. Among them, flavonoids are considered to be the most promising compounds because of their prominent iron chelation. Mechanically, these herbal medicines act on the Nrf2 signaling pathway, AMPK signaling pathway, and KAT5/GPX4 signaling pathway, thereby attenuating iron overload and lipid peroxidation in CVD. Our review provides up-to-date information on herbal medicines that exert cardiovascular protective effects by modulating iron overload and ferroptosis. These herbal medicines hold promise as a template for preventing iron overload in CVD.