Abstract

Ethnopharmacological relevance Qufeng Xuanbi Formula (QFXBF), a traditional Chinese medicine prescription used for asthma-like respiratory disorders, has shown anti-asthmatic activity. However, whether it attenuates allergic airway remodeling through innate immune-metabolic regulation remains unknown. Aim of the study This study aimed to determine whether QFXBF alleviates house dust mite (HDM)-induced allergic airway inflammation and remodeling through targeting the STING/HIF-1α/glycolysis axis, and to evaluate the specific inhibitory potential of its constituent tectorigenin on STING-mediated immunometabolic signaling. Materials and methods An HDM-induced allergic asthma model was established in male C57BL/6 mice by intranasal sensitization and challenge, followed by oral administration of QFXBF at 12.5, 25, and 50 g/kg/day or dexamethasone at 2 mg/kg/day. Airway hyperresponsiveness, lung histopathology, mucus secretion, collagen deposition, α-SMA expression, inflammatory mediators in BALF and serum, and glycolytic metabolic indices were evaluated. BSMCs were stimulated with IL-4 and LPS, both at 5 ng/mL, and treated with QFXBF at 2, 4, and 8 mg/mL. Cell proliferation, migration, glucose consumption, lactate production, RT-qPCR, Western blotting, and immunofluorescence were performed to assess airway smooth muscle activation and metabolic reprogramming. Transcriptomic analysis of lung tissue, STING overexpression, HIF-1α pharmacological inhibition, LC-MS/MS-based identification of tectorigenin, molecular docking, and molecular dynamics simulations were further used to investigate the STING/HIF-1α/glycolysis axis and the potential STING-targeting activity of tectorigenin. Results QFXBF markedly reduced airway hyperresponsiveness, inflammatory infiltration, and collagen deposition in HDM-challenged mice, accompanied by decreased asthma-related markers in bronchoalveolar lavage fluid and serum. QFXBF also downregulated STING, HIF-1α, and key glycolytic enzymes at bot