Investigation of the active compounds and pharmacological mechanisms of Qufengxuanfei decoction in the treatment of chronic cough

ObjectiveTo investigate the mechanism of the Qufengxuanfei Decoction (QFXFD) in improving airway neurogenic inflammation in chronic cough through network pharmacology and animal experiments.MethodsThe active components and potential targets of QFXFD were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease-related targets associated with chronic cough were retrieved from the GeneCards, OMIM, and TTD. The intersection of drug targets and disease targets was determined, and a “TCM–bioactive compounds–intersection targets” network was constructed using Cytoscape software. Protein–protein interaction (PPI) analysis of the intersecting targets was performed via the STRING database to identify core genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were subsequently conducted. Molecular docking was performed using AutoDock and related tools to validate the interactions between key active compounds and core targets. A guinea pig model of heightened cough sensitivity was established, followed by intervention with QFXFD. Cough frequency, differential cell counts in bronchoalveolar lavage fluid (BALF), and histopathological changes in lung tissue were evaluated. In addition, the expression levels of PLC-β, PKC, TRPA1, TRPV1, and SP/NK-1R in lung tissues were assessed.ResultsThe key bioactive constituents of QFXFD responsible for alleviating airway neurogenic inflammation in chronic cough were identified as quercetin, β-sitosterol, luteolin, kaempferol, stigmasterol, and tanshinone IIA. A total of 207 intersecting targets between QFXFD and chronic cough were identified, with core targets including TP53, AKT1, IL6, MAPK1, MAPK3, TNF, BCL2, CASP3, ESR1, CCND1, HSP90AA1, and MYC. These shared targets were significantly enriched in 838 biological processe (BP), 188 molecular function (MF), 104 cellular component (CC), and 179 KEGG pathways. Molecular docking analyses demonstrated favorable binding affinities between tanshinone IIA and TP53, luteolin and TP53, kaempferol and TNF, as well as quercetin and TNF. Animal experiments showed that the QFXFD could significantly improve the peripheral cough hypersensitivity state of guinea pigs with increased cough sensitivity, reduce the frequency of cough, decrease the proportion of neutrophils and eosinophils in BALF, improve the pathological damage of lung tissue, and also reduce the expression levels of PLC-β, PKC, TRPA1, TRPV1, and SP/NK-1R.ConclusionQFXFD exerts its therapeutic effects through a multi-component, multi-target, and multi-pathway mechanism. Its diverse active constituents modulate a variety of signaling pathways and regulate key biological processes related to inflammation and immune responses, thereby contributing to the improvement of airway neurogenic inflammation and airway hyperresponsiveness. These findings provide a valuable theoretical and experimental basis for the clinical application and further development of QFXFD as a potential therapeutic strategy for chronic cough.