Ferroptosis: A Novel Mechanism and Therapeutic Target of Traditional Chinese Medicine for Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent chronic liver disorder, with its progression closely linked to ferroptosis, an iron-dependent, lipid peroxidation-driven form of regulated cell death. This review systematically elucidates the core mechanisms of ferroptosis in MASLD, emphasizing its spatiotemporal heterogeneity across disease stages and its role as a key pathological bridge connecting metabolic dysfunction to hepatic injury, inflammation, and fibrosis. Furthermore, we highlight the unique advantages of Traditional Chinese Medicine (TCM) in modulating ferroptosis through multi-component, multi-target, and multi-pathway approaches. TCM active ingredients and compound formulations can intervene at molecular, metabolic, and microenvironmental levels, regulating iron homeostasis, inhibiting lipid peroxidation, enhancing antioxidant defenses, and remodeling the hepatic immune-metabolic crosstalk. Building on these insights, we propose a precision intervention framework centered on "Temporal-Spatial-Pathogenesis", which integrates TCM's holistic and syndrome-based principles with modern precision medicine concepts. This framework aims to guide stage-specific and cell-type-targeted strategies for MASLD treatment, offering new directions for TCM modernization and the development of novel therapeutic approaches targeting ferroptosis in metabolic liver diseases.