Total Astragalus Saponins Modulate Ferroptosis Pathways in Cigarette Smoke and LPS-Induced Models of COPD: An in vitro and in vivo Investigation.

Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by persistent airflow limitation and chronic airway inflammation. Emerging evidence indicates that ferroptosis contributes to disease pathogenesis. The current therapeutic strategies cause adverse side effects and frequent exacerbations. Methods: A COPD murine model was developed through exposure to cigarette smoke (CS) and lipopolysaccharide (LPS). We evaluated the impacts of AST on respiratory function, pulmonary index, lung pathology, and serum reactive oxygen species (ROS) and glutathione (GSH) levels in the COPD mice. Beas-2B cells were stimulated with cigarette smoke extract (CSE) to evaluate GSH, malondialdehyde (MDA), ROS, lipid peroxidation, Fe Results: In COPD mice (n=8), AST treatment significantly improved respiratory function (Penh, TV, EF50, EF75), reduced tracheal wall thickening and inflammatory cell infiltration ( Conclusion: Our findings suggest that AST exerts protective effects against CS and LPS-induced COPD in mice and CSE-induced injury in Beas-2B cells that are associated with modulation of ferroptosis-related markers. These results provide preliminary evidence supporting continued investigation of AST in preclinical COPD models and offer potential directions for future mechanistic research.