Epigenetic Regulation of Ferroptosis in Inflammation: Molecular Mechanisms and Therapeutic Perspectives

Ferroptosis is an iron-dependent form of regulated cell death characterized by the lethal accumulation of lipid peroxides and has emerged as an important contributor to the initiation, progression, and amplification of inflammatory responses. DNA methylation, histone modifications, and noncoding RNA-mediated regulation influence ferroptosis by modulating multiple molecular pathways, thereby shaping the inflammatory microenvironment. Active constituents and compound formulas of traditional Chinese medicine (TCM) exhibit multi-target, multi-pathway regulatory properties that enable the simultaneous regulation of epigenetic modifications, ferroptosis, and inflammation. However, the molecular mechanisms linking these processes have not been systematically summarized. This review discusses the molecular mechanisms underlying ferroptosis, the epigenetic mechanisms that regulate ferroptosis, and the reciprocal interplay between ferroptosis and inflammation. It further highlights recent advances in understanding how active constituents and compound formulas of TCM modulate ferroptosis through epigenetic regulation to alleviate inflammatory injury. By integrating current evidence, this review provides mechanistic insights into the epigenetic basis of the anti-inflammatory actions of TCM and underscores the therapeutic potential of epigenetic modulation of ferroptosis for the treatment of inflammatory diseases.