基于UPLC-Q-Exactive Orbitrap-MS和网络药理学结合动物实验探讨干姜拌捣五味子治疗痰饮哮喘的作用机制OA

The effects of Zingiberis Rhizoma mixed and triturated with Schisandrae Chinensis Fructus(ZMTS)on phlegm asthma were investigated based on compositional analysis,network pharmacology,and animal experiments.The compositional analysis of ZMTS using UPLC-Q-Exactive Orbitrap-MS identified a total of 37 components,with 33 active components screened out by TCMSP and SwissADME.SwissTargetPrediction and Superpred were employed to search for targets corresponding to the active components,while GeneCards was used to search for targets of the active constituents,resulting in a total of 118 intersection targets.The protein-protein interaction(PPI)network of component-disease intersection targets was constructed using STRING 11.0 and visualized using Cytoscape 3.10.0.The DAVID platform was utilized to perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses on the intersection targets,revealing that the phosphatidylinositide 3-kinase/protein kinase B(PI3K/Akt)pathway was an important therapeutic pathway.A component-target-pathway network was constructed,and the core components and core targets were subjected to molecular docking,demonstrating a good binding effect between the core components and core targets.The mechanism of action of ZMTS was verified by establishing a mouse model of phlegm asthma through histopathological staining,immunohistochemistry(IHC),enzyme-linked immunosorbent assay(ELISA),and Western blot.The animal experiments showed that the high-dose ZMTS group could significantly improve the airway inflammatory response in the mice with phlegm asthma,reduce the levels of interleukin-17(IL-17)and interleukin-23(IL-23),and significantly inhibite the phosphorylation level of PI3K and Akt proteins.ZMTS exerts its effect in improving phlegm asthma by acting on targets such as IL-17 and IL-23 through multiple components,with the mechanism closely related to the regulation of PI3K/Akt signaling pathway,fully demonstrating the comprehensive effect of multi-components,multi-targets,and multi-pathways.