Mechanism and Validation of Jupi Zhuru Decoction in the Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting Based on Network Pharmacology
Objective:To predict the active ingredients,target genes,and signaling pathways of Jupi Zhuru Decoction in preventing and treating chemotherapy-induced nausea and vomiting(CINV)based on network pharmacology,and to explore its anti-emetic mechanism through molecular docking and animal experiments.Methods:The active ingredients of Jupi Zhuru Decoction were se-lected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Ctd data-base.CINV-related target genes were obtained from the Uniprot,DisGeNET,and GeneCard databases.Network fitting and screening were performed between the active ingredients and CINV-related targets.The active ingredient-target-disease network was construc-ted using Cytoscape software,and protein-protein interaction(PPI)network was built using the String database and topological anal-ysis was conducted.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were visu-alized using Metascape and MicroBing databases,followed by identification of key proteins.Molecular docking validation was per-formed using AutoDock and PYMOL software.In animal experiments,rats were modeled for CINV and treated with the drug.The kaolin intake of rats was measured,and histopathological changes in the medulla oblongata and ileum were observed.The expression levels of protein kinase B(AKT),glycogen synthase kinase-3β(GSK-3β),serotonin(5-HT),tryptophan hydroxylase(TPH),and monoamine oxidase A(MAOA)were assessed.Results:A total of 141 active ingredients from Jupi Zhuru Decoction were identi-fied,and 79 intersection genes between the compound and disease were obtained,with 9 core targets.The anti-emetic effects may be related to the induction of AKT membrane translocation and inhibition of GSK-3 phosphorylation at Ser9/21.Animal experiments showed that Jupi Zhuru Decoction reduced kaolin intake and alleviated intestinal inflammation in CINV rats.It also upregulated AKT levels in the medulla oblongata and ileum,inhibited GSK-3 expression,suppressed TPH synthesis in the medulla oblongata and ileum,and promoted the secretion of MAOA,resulting in reduced 5-HT expression.Conclusion:Jupi Zhuru Decoction can pre-vent and treat CINV by regulating the AKT/GSK-3β signaling pathway to inhibit GSK-3β expression in the medulla oblongata and ileum.It also inhibits TPH synthesis and promotes MAOA secretion,achieving anti-emetic effects.
万方数据
维普
