基于GEO数据库、网络药理学和分子动力学模拟探究御寒汤治疗过敏性鼻炎的作用机制OA

Objective:To investigate the mechanism of action of Yu Han Tang(御寒汤)for the treatment of allergic rhinitis(AR)based on GEO database,network pharmacology and molecular dynamics simulation.Methods:TCMSP database was used to search the active ingredients and targets of Yu Han Tang.The targets were converted into gene symbols by UniProt database,and the related targets of AR were retrieved by GeneCards,OMIM,TTD,and DrugBank databases.The regulatory network was constructed by CytoScape,the PPI network was constructed by STRING database,and the core genes were screened.The core genes were further screened using machine learning.GO and KEGG enrichment analysis was performed using R language.Molecular docking validation of core components and core targets was performed using AutoDockVina 1.1.2,and the results with the lowest binding energy were selected for molecular dynamics simulation.Immune infiltration analysis was performed using the CIBERSORT(R package),and the correlation between core genes and immune cells was analyzed.Finally,the distribution and expression of major cell subpopulations and core genes were identified by single-cell analysis.Results:A total of 200 active ingredients and 250 potential targets were screened,2 546 allergic rhinitis-related targets were identified,and 120 potential targets were derived after taking the intersection.The core targets were mainly BcL-2,ESRI,IFNG,IL-4,MAPK14,NFKBIA,and STAT3.Drug-Active Ingredient-Target network yielded core ingredients mainly quercetin,kaempferol,luteolin,7-O-methylisomucronulatol,β-sitosterol,wogonin,etc.GO enrichment analysis showed reactions involving response to molecule of bacterial origin,membrane raft,etc.KEGG pathway enrichment analysis showed mainly related to IL-17,TNF,HIF-1 signaling pathways.Molecular docking showed that all the core components could spontaneously bind to target,and molecular dynamics simulation indicated that luteolin could stably bind to the target protein ESRI.Conclusion:Yu Han Tang can treat AR through multi-component,multi-target and multi-pathway.