Research on the Mechanism of Zhiwei Fuwei Pill Intervention in Precancerous Lesions of Gastric Cancer Based on Network Pharmacology and Experimental Validation
Objective To explore the potential mechanism of Zhiwei Fuwei Pill in intervening precancerous lesions of gastric cancer (PLGC) by network pharmacology,molecular docking technology and animal experiments. Methods The active components and corresponding targets of Zhiwei Fuwei Pill were screened by traditional Chinese medicine database and analysis platform (TCMSP) and related literature,and the disease targets of PLGC were screened by GeneCards database. The intersection target of the two targets was the potential target of Zhiwei Fuwei Pill in the treatment of PLGC. Cytoscape software was used to construct the"drug-active ingredients-targets"network,and STRING database was applied to establish the protein interaction network,and then the key active ingredients and key targets were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the intersection targets using the DAVID database. AutoDockTools software was used to verify the molecular docking of key active ingredients and key targets. PLGC model was replicated by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)and other comprehensive factors. HE staining was used to detect the pathological changes of gastric tissue. Western Blot was used to detect the protein expression of PI3K,AKT,TNF-α,IL-6 and Caspase-3 in gastric tissue. Results A total of 258 active components,325 corresponding targets,1294 disease targets and 139 intersection targets (potential targets)of Zhiwei Fuwei Pill were obtained. The key active ingredients were quercetin,luteolin,kaempferol,beta-sitosterol,etc. The key targets were AKT1,CASP3,IL-6,TNF,etc. There were 950 GO-related items and 177 KEGG-related pathways,mainly involving PI3K/AKT,MAPK,IL-17,TNF and apoptosis. Molecular docking showed that good binding activity and stability between quercetin,luteolin,kaempferol,and beta-sitosterol and the top 10 key targets in terms of degree value(AKT1,TP53,CASP3,IL-6 and TNF,etc.) were found. The results of animal experiments showed that compared with the model group,the pathological morphology of gastric tissue in rats of Zhiwei Fuwei Pill group was significantly improved. Simultaneously,the expression levels of PI3K,p-PI3K,AKT,p-AKT,TNF-α and IL-6 in gastric tissue of rats in this group were significantly decreased (P<0.05,P<0.01),and the expression of Caspase-3 protein was significantly increased (P<0.01). Conclusion Zhiwei Fuwei Pill has the characteristics of multi-components,multi-targets and multi-pathways in the treatment of PLGC. It can play an intervention role by inhibiting inflammatory response and promoting apoptosis,which may be related to the regulation of PI3K/AKT signaling pathway.
万方数据
维普
