Integrated proteomics and metabolomics analysis reveals mechanisms by which SFYC decoction regulates airway inflammation in asthma.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Airway inflammation is one of the primary pathological characteristics of asthma. Soufeng Yuchuan (SFYC) decoction, a compound formula derived from multiple traditional Chinese medicine prescriptions, is widely applied clinically and exhibits significant therapeutic efficacy against asthma. However, its anti-asthmatic mechanisms remain incompletely understood. MATERIALS AND METHODS: Asthmatic rat models induced by ovalbumin (OVA) and ferroptosis models induced by erastin in BEAS-2B cells were established. Proteomics and metabolomics analyses were conducted on lung tissues and serum. Key ferroptosis-related targets (GPX4, SLC7A11/SLC3A2, GCLC, GSS, and VDAC2) were validated using Western blotting, RT-qPCR, and biochemical assays. The direct anti-ferroptosis effects of SFYC-containing serum were compared with ferrostatin-1 and blank serum in vitro. RESULTS: Integrated omics analysis revealed that ferroptosis, glutathione metabolism, and ROS signaling pathways were the core targets modulated by SFYC. In vivo, SFYC significantly reduced airway inflammation and ROS accumulation, restored pulmonary GSH levels, upregulated the expression of GPX4, GCLC, GSS, SLC7A11, and SLC3A2, and downregulated VDAC2 expression (P&#xa0;<&#xa0;0.05). In vitro, SFYC-containing serum effectively reversed erastin-induced lipid peroxidation, iron overload, GSH depletion, ROS elevation, and apoptosis in BEAS-2B cells, demonstrating comparable or superior efficacy to ferrostatin-1. CONCLUSION: SFYC alleviates airway inflammation in asthma primarily by inhibiting ferroptosis. This study provides evidence that SFYC exerts anti-asthmatic effects, at least in part, via the regulation of ferroptosis pathways.