Xiaoqinglong Decoction Attenuates Allergic Rhinitis Comorbid with Asthma via Modulation of the ALOX15/GPX4 Axis

OBJECTIVE: Xiaoqinglong Decoction (XQLD) is a classical traditional Chinese medicine (TCM) formula for allergic rhinitis (AR) and asthma. However, its underlying therapeutic mechanisms in allergic rhinitis comorbid with asthma (ARCA) remain elusive. This study employed proteomics to investigate the therapeutic effects and molecular mechanisms of XQLD in ARCA, aiming to provide a scientific basis for clinical research. METHODS: Forty BALB/c mice were randomly divided into four groups: control, model, dexamethasone-treated, and XQLD-treated. An ARCA model was established using ovalbumin (OVA) and aluminium hydroxide. Airway allergic symptoms, serum levels of OVA-sIgE, and histopathological changes in nasal and lung tissues were assessed. Flow cytometry was performed to analyze the proportions of Th1 (CD4 + IFN-γ+) and Th2 (CD4 + IL-5+) cells in lung and spleen tissues. Proteomic analysis was conducted to identify differentially expressed proteins, which were subsequently subjected to GO and KEGG pathway enrichment analyses. The expression levels of ALOX15 and GPX4 were validated using western blotting and immunofluorescence staining. RESULTS: ARCA model mice exhibited increased airway allergic symptom score and serum OVA-sIgE levels, accompanied by marked inflammatory cell infiltration and goblet cell hyperplasia in nasal and lung tissues. A pronounced Th1/Th2 imbalance was observed, characterized by elevated frequencies of Th1 and Th2 cells and a decreased Th1/Th2 ratio. Additionally, ARCA model mice showed upregulated ALOX15 expression and downregulated GPX4 expression. Treatment with XQLD ameliorated these pathological and immunological abnormalities. CONCLUSIONS: XQLD alleviates allergic airway inflammation and tissue remodelling in ARCA, potentially by restoring the ALOX15/GPX4 axis-mediated equilibrium between lipid peroxidation and antioxidant defence systems.