Network Pharmacology Combined with Animal Experiments Elucidates the Mechanism of Effect of Xin’an Formula in Treating Allergic Rhinitis

Ming Zhang,1 Ruohui Song2 1Department of Otorhinolaryngology, The First School of Clinical of Anhui University of Chinese Medicine, Hefei, Anhui, 230012, People’s Republic of China; 2Department of Otorhinolaryngology, The First Affiliated Hospital of Anhui University of CM, Hefei, Anhui, 230031, People’s Republic of ChinaCorrespondence: Ruohui Song, Department of Otorhinolaryngology, The First Affiliated Hospital of Anhui University of CM, 117 Meishan Road, Shushan District, Hefei, Anhui, 62850080, People’s Republic of China, Email [email protected]: Exploring the mechanism of the effect of Xin’an BiYan Formula (XBY) in treating allergic rhinitis (AR) using network pharmacology combined with animal experiments.Methods: Key targets for AR treatment were identified through multi-database and PPI network screening. Potential signaling pathways were predicted by conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The predicted targets and pathways in animal experiments to learn XBY’s effects on inflammation and apoptosis in nasal mucosal tissue cells during AR development.Results: Screening identified 18 principal targets of XBY in AR: TNF, AKT1, HIF1A, MMP9, BCL2, EGFR, IL-2, PTGS2, VCAM-1, PTGS1, ACE, PPARG, ICAM-1, SIRT1, ITGB1, JAK2, RELA, and KIT. The key pharmacological constituents included Genkwanin, Calycosin, Kaempferol, and Luteolin. GO and KEGG enrichment analyses revealed significant enrichment in the PI3K/AKT, Apoptosis, and NF-kappa B signaling pathways. After XBY treatment, infiltration of eosinophils (EOS) and mast cells (MC) in the nasal mucosa of AR model mice was reduced. Concurrently, serum levels of IL-6, TNF-α, COX-2, Total-IgE, OVA-IgE, ICAM-1, and VCAM-1 were decreased. Mucosal levels of p-PI3K/PI3K, p-AKT/AKT, p-n-p65/c-p65, p-IKKβ/ IKKβ, and Bcl-2 proteins were decreased, while Bax, Cleaved-Caspase3, and Caspase-3 protein expression were increased. Cellular levels of reactive oxygen species(ROS) and apoptosis levels were reduced.Conclusion: The experimental results indicate that the therapeutic effect of XBY on AR is likely mediated through modulation of the ROS/PI3K/AKT/NFκB signaling pathway. By reducing inflammatory cell infiltration, downregulating the expression of inflammatory and adhesion factors, and modulating apoptosis proteins to accelerate inflammatory cell apoptosis, dual mechanisms effectively inhibit the progression of inflammation. This study holds potential translational prospects and may provide new insights for the treatment of AR with TCM.Keywords: network pharmacology, allergic rhinitis, traditional Chinese medicine, PI3K/AKT signaling pathway, inflammation