Qixian Decoction Improves Airway Hyperresponsiveness by Inhibiting TRPV1 and Downstream PI3K-Akt/HIF-1α Signaling

Introduction: Qixian Decoction (QXT), a traditional Chinese medicine formula, exerts favorable therapeutic effects on asthma, but its underlying mechanisms remain incompletely elucidated. Materials and Methods: This study combined network pharmacology and experimental validation. Employing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we screened active compounds of QXT and their targets. A herbcompound- target network was constructed. DEGs were recognized from the GSE161245 asthma dataset. Molecular docking was utilized to validate the interaction of key compounds with selected core targets. The effects of QXT on the Potential Vanilloid 1 (TRPV1)/Phosphatidylinositol 3-Kinase-Protein Kinase B (PI3K-Akt)/Hypoxia-Inducible Factor-1α (HIF-1α) axis and Epithelial- Mesenchymal Transition (EMT) were evaluated using in vivo (asthmatic mice) and in vitro (TGF-β-stimulated 16HBE cells) models. results: Eighty-three active ingredients and 308 potential targets were identified, with PI3K-Akt pathway significantly enriched. Key targets (IGF1R, CDK6, EGFR) positively correlated with TRPV1. Luteolin, quercetin, and EGCG stably bound to their targets. QXT suppressed TRPV1, p-AKT, and HIF-1α, and ameliorated airway hyperresponsiveness and EMT in vivo and in vitro. Results: A total of 83 active compounds and 308 potential targets were identified, with significant enrichment observed in the PI3K-Akt pathway. Key targets (IGF1R, CDK6, and EGFR) were positively correlated with TRPV1. Luteolin, quercetin, and EGCG stably bind to their targets. QXT suppressed TRPV1, p-AKT, and HIF-1α, and ameliorated airway hyperresponsiveness and EMT in vivo and in vitro. Discussion: QXT could alleviate asthma airway hyperresponsiveness and remodeling by inhibiting the TRPV1/PI3K-Akt/HIF-1α axis and EMT. The active compounds potentially exerted their therapeutic effects through multi-target mechanisms. Conclusion: QXT alleviated asthma airway remodeling and hyperresponsiveness via suppressing the TRPV1/PI3K-Akt/HIF-1α signaling axis and EMT, providing a scientific basis for its clinical application.