Study on the mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pha

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Objective: To explore the main active components and mechanism of Guizhi Fuling pill in the treatment of ovarian cancer based on network pharmacology and molecular docking technology. Methods: TCMSP database was used to retrieve and screen the active components of each Chinese medicine in Guizhi Fuling pill. The main active components of the medicine were screened through the network analysis function of Cytoscape software, and the target of the main active components of the medicine was found in UniProt database. Using genecards, OMIM, digsee, TTD, and drugbank database to retrieve the related targets of ovarian cancer. The interaction between the target of the main active components of the drug and the related target of ovarian cancer was obtained by R software. The intersection targets are imported into string database for PPI analysis, and then the results are imported into Cytoscape to get the hub gene using the cyclohubba plug-in. KEGG pathway analysis and go enrichment analysis were carried out in metascape database. At last, autodock tools was used to verify the main active ingredients and the selected target proteins. PyMOL and LigPlus software visualized the results. Results: The main active components of Guizhi Fuling pills were quercetin, β- sitosterol, kaempferol, hederagenin, catechin, ellagic acid, stigmasterol and Douglas fir. There are 20 pivotal genes of drug effect on ovarian cancer, including VEGFA, AKT1, mapk8, Jun, MMP9, IL6, TNF, CXCL8, PTGS2, TP53, CASP3, mapk1, EGF, ESR1, EGFR, Myc, FOS, CCL2, CXCL8 and IL1B. According to KEGG pathway analysis, 10 pathways with the highest correlation were found: cancer signaling pathway, MAPK signaling pathway, fluid shear stress and atherosclerosis, hepatitis B, trypanosomiasis, age-rage signaling pathway in diabetic complications, tumor necrosis factor signaling pathway, pertussis, IL-17 signaling pathway, and bladder cancer. Go enrichment analysis has screened out 10 important items in molecular biological function, cell components and biological process. The proteins encoded by IL6, mapk1, VEGFA, AKT1, TP53, TNF and CCL2 were used as targets to dock with the main active components of the drug respectively, and the best results were TNFαand ellagic acid. Conclusion: The main active components of Guizhi Fuling pill regulate multiple signal pathways by regulating IL6, VEGFA, CCL2, TNF, MMP9 and other cytokines, and inhibit the proliferation and metastasis of cancer cells.
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