Modulation of Ferroptosis: A Novel Mechanism of Traditional Chinese Medicine in Managing Chronic Atrophic Gastritis

Chronic atrophic gastritis (CAG) is a major precancerous lesion of gastric cancer, characterized by a high incidence rate, a protracted clinical course, and a well-documented risk of malignant transformation. Current Western medical treatments exert limited efficacy in reversing progressive gastric mucosal damage. In traditional Chinese medicine (TCM), CAG is categorized as expressing symptoms such as “stomachache” and “abdominal fullness,” with the core pathogenesis defined as “spleen–stomach deficiency as the root, and qi stagnation, blood stasis, and damp-heat as the superficial manifestations.” TCM confers distinct clinical advantages through therapeutic strategies which include invigorating the spleen and replenishing qi, clearing heat and resolving dampness, and promoting blood circulation to remove stasis. Ferroptosis, an iron-dependent form of regulated cell death, has been increasingly recognized as a key driver of gastric mucosal injury and disease progression in CAG, and exerts its effects via nine core pathways including iron metabolism imbalance, glutathione (GSH) depletion, lipid peroxidation (LPO), mitochondrial dysfunction, and inflammatory responses. This review systematically elaborates on the molecular mechanisms of ferroptosis in CAG pathogenesis and comprehensively summarizes recent advances in how active ingredients derived from Chinese herbal medicines (such as baicalein, curcumin, tanshinone IIA, astragaloside IV) and classic compound formulas like Sijunzi Decoction, Banxia Xiexin Decoction, Moluodan, and Weifuchun regulate ferroptosis-related signaling pathways. It further highlights the multi-target, multi-pathway characteristics of TCM in alleviating oxidative damage and promoting mucosal repair. Ultimately, this review aims to elucidate the scientific basis of TCM-mediated ferroptosis regulation in CAG management, provide novel theoretical support for clinical practice, and guide future directions for drug research and development.