Traditional Chinese Medicine Modulates Ferroptosis to Manage Chronic Atrophic Gastritis

Chronic Atrophic Gastritis (CAG) is a significant precancerous lesion for gastric cancer, characterized by high incidence, protracted course, and a well-documented risk of malignant transformation. Current Western medical treatments often fall short in reversing progressive gastric mucosal damage. Ferroptosis, an iron-dependent form of regulated cell death, has emerged as a crucial driver of gastric mucosal injury and disease progression in CAG, making its modulation a promising therapeutic target.

This review systematically elaborated on the molecular mechanisms of ferroptosis in CAG pathogenesis. Researchers comprehensively summarized recent advances in how active ingredients derived from Chinese herbal medicines, such as baicalein, curcumin, tanshinone IIA, and astragaloside IV, along with classic compound formulas like Sijunzi Decoction, Banxia Xiexin Decoction, Moluodan, and Weifuchun, regulate ferroptosis-related signaling pathways. The work aimed to elucidate the scientific basis of TCM-mediated ferroptosis regulation in CAG management.

Ferroptosis, an iron-dependent form of regulated cell death, is a key driver of gastric mucosal injury and disease progression in Chronic Atrophic Gastritis (CAG). This process is mediated via nine core pathways, including iron metabolism imbalance, glutathione (GSH) depletion, lipid peroxidation (LPO), mitochondrial dysfunction, and inflammatory responses. The review found that active ingredients from Chinese herbal medicines, such as baicalein, curcumin, tanshinone IIA, and astragaloside IV, effectively regulate these ferroptosis-related signaling pathways. Classic TCM compound formulas like Sijunzi Decoction and Weifuchun also demonstrate significant modulatory effects on ferroptosis. This multi-target, multi-pathway characteristic of TCM helps alleviate oxidative damage and promotes mucosal repair.

The systematic review highlights that TCM interventions can regulate ferroptosis by targeting iron metabolism, GSH synthesis, lipid peroxidation, and mitochondrial function, providing a comprehensive approach to CAG management.