Soufeng Yuchuan formula alleviates asthma airway inflammation and suppresses the progression of asthma by inhibiting ferroptosis in airway epithelial cells.

OBJECTIVE: To explore whether Soufeng Yuchuan (, SFYC) formula alleviates asthma by promoting ferroptosis of airway epithelial cells. METHODS: A chronic asthma rat model was established using ovalbumin (OVA) combined with aluminum hydroxide sensitization and OVA nebulization stimulation. Lung tissue pathology was assessed via hematoxylin and eosin staining and periodic acid-Schiff staining. Lung tissue ultrastructure was observed using transmission electron microscopy. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. Malondialdehyde (MDA), glutathione, and tissue ferrous ion content in rat lung tissues and cells were detected using commercial kits. Immunohistochemical staining was used to determine the expression levels of interleukin-13 (IL-13) and interleukin-6 (IL-6) in lung tissue. Western blotting was employed to detect the expression levels of transferrin receptor 1 (TFR1), transferrin receptor 2 (TFR2), acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). Cell proliferation, apoptosis and reactive oxygen species (ROS) were evaluated using a cell counting kit-8 assay and flow cytometry. Intracellular lipid peroxidation was detected using a C11-BODIPY 581/591 (C11-BODIPY) probe. RESULTS: SFYC formula effectively alleviates airway inflammation in asthmatic rats in a dose-dependent manner. It improves airway epithelial cell integrity, reduces alveolar wall thickening and expansion, inhibits goblet cell proliferation and mucus secretion, and decreases the expression of IL-6 and IL-13 in lung tissue, as well as the serum levels of IL-6, IL-13, interleukin-4 (IL-4), and immunoglobulin E (IgE). SFYC formula mitigates ferroptosis in lung tissue of asthmatic rats. At the cellular level, it promotes proliferation of rat airway epithelial cells, inhibits cell apoptosis, suppresses ROS, MDA, and lipid accumulation, reduces the expression of TFR1, TFR2, and ASCL4, and increases the expression of GPX4 and SLC7A11 to mitigate ferroptosis. CONCLUSION: SFYC formula alleviates asthma airway inflammation by inhibiting ferroptosis in airway epithelial cells, providing new insights and potential therapeutic targets for the development of new asthma treatment drugs.