Study On The Mechanism Of Action Of Ecan Jianwei Prescription In Treating Gastric Precancerous Lesions Based On Network Pharmacolog

Objective:To study the effective components and possible targets of Ecanjianwei Decoction in the treatment of gastric precancerous lesions by means of network pharmacology,and to explore the mechanism of Ecanjianwei Decoction in the treatment of gastric precancerous lesions.Methods:The effective components of Ecanjianwei Decoction were screened from the TCMSP platform,TCMID database,and BATMAN-TCM database,and the obtained effective components were input into ETCM to query their target points.Obtain the targets related to gastric precancerous lesions through Gene Cards database and OMIM database.Take the intersection of drug targets and disease-related targets to obtain potential targets of Ecanjianwei Decoction in treating gastric precancerous lesions.The Cytoscape software is used to construct a drug-active ingredient-target-disease network for the treatment of gastric precancerous lesions by Ecanjianwei Decoction.Use the Network Analysis plug-in under the Tools column of Cytoscape software to perform topological analysis on the network,and screen out the core effective ingredients of Ecanjianwei Decoction in the treatment of gastric precancerous lesions.Obtain the high-confidence interaction relationship of Ecanjianwei Decoction in the treatment of gastric precancerous lesions in the STRING database,and construct its interaction network in Cytoscape.Use the Network Analysis plug-in to analyze the network topology and screen out the core targets of Ecanjianwei Decoction in the treatment of gastric precancerous lesions.Obtain the structure of some core target proteins in the RCSB PDB database,use Auto Dock Vina software to verify the molecular docking of some core target proteins and some core active ingredients,and use Py MOL software to visualize the docking results.Use the DAVID database to analyze the GO function and KEGG pathway enrichment analysis of the potential targets of Ekanjianwei Decoction in the treatment of gastric precancerous lesions,and construct a drug-active ingredient-target-pathway network diagram in Cytoscape.1 Effective ingredients and targets of Ecanjianwei Decoction: A total of 192 active ingredients of Ecanjianwei Decoction were obtained from the TCMSP database,TCMID database,and BATMAN-TCM database.The potential effects of Ecanjianwei Decoction were queried in the ETCM database.There are 278 kinds of targets.2 Related targets and intersection targets for gastric precancerous lesions: Based on the Gene Cards database and the OMIM database,2113 related targets for gastric precancerous lesions were obtained.There are a total of 73 targets at the intersection of drugs and diseases.3 The drug-active ingredient-target-disease network of Ecanjianwei Decoction for the treatment of gastric precancerous lesions: The drug-active ingredient-target-disease network of Ecanjianwei Decoction for the treatment of gastric precancerous lesions is constructed by Cytoscape software.There are 125 nodes and 986 edges in the network,including 1 disease node,14 drug nodes,37 active ingredient nodes,and 73 target nodes.Topological analysis of the network shows that the median value of node Degree is 10,the median of betweenness centrality is 0.00511408,and the median of close centrality is 0.41196013.After screening,a total of 15 core active ingredients in the treatment of gastric precancerous lesions of Ecanjianwei Decoction were obtained.The core active ingredients of are kaempferol,oxaxanthin,luteolin,baicalein,baicalin,triptolide,isorhamnetin,holy grass phenol,naringenin,geraniol,orange Cortexin,(+)-catechol,6-methoxynaringenin,wogonin,plantain.4 Potential target PPI network: Obtain the high-confidence interaction relationship of Ecanjianwei Decoction in the treatment of gastric precancerous lesions related proteins from the STRING database,and construct its PPI network in Cytoscape.Excluding the targets that have no effect on other targets,there are a total of 61 nodes and 163 edges in the PPI network.The larger the diameter and the darker the color of the node in the graph,the greater the degree value of the node.The topology analysis of the PPI network is performed,and the results of the topology analysis of the PPI network are shown in Table 4.The median of the Degree value is twice as large as 6,the median of BC is 0.00579838,and the median of CC is 0.34117647.A total of 20 targets that meet the screening conditions of the core targets were found,namely IL6,AKT1,HSP90AA1,HSP90AA1,TNF,PTGS2,ESR1,INS,RXRA,PPARG,CEBPB,IL1 B,NFKB1,AR,NOS2,AHR,RXRB,PPARA,CSNK2A1,JAK1,HDAC2.Results:5 Part of the core target and core active ingredient molecular docking simulation verification: download the molecular structure of the core active ingredient in the Pub Chem database,download the protein file of the core target in the RCSB PDB database,and simulate the docking of the two through the Auto Dock Vina software,And visualize the docking results.The results calculated that the binding energy between the target protein and the active ingredient was less than-5.0kcal·mol,indicating that the receptor protein and the active ingredient have binding activity and can form a relatively stable conformation.6 GO function and KEGG pathway enrichment analysis results: GO function enrichment analysis in the DAVID database,a total of 360 entries were obtained,including 256 entries for biological processes(BP)and 38 cellular components(CC)BP analysis showed that the potential targets are mainly involved in the initial transcription of RNA polymerase II promoter,the positive regulation of nitric oxide biosynthesis process,the positive regulation of RNA polymerase II promoter transcription,the intracellular receptor signaling pathway,and the positive regulation of nitric oxide biosynthesis,regulation of drug response,etc;CC analysis shows that potential targets are mainly distributed in the nucleoplasm,nucleus,cytoplasm,basolateral plasma membrane,and cytoplasmic perinuclear regions;MF analysis shows that potential targets are mainly involved in RNA polymerase II transcription Factor activity,ligand-activated sequence-specific DNA binding,transcription factor binding,sequence-specific DNA binding,protein binding,etc.KEGG pathway enrichment analysis yielded a total of 30 signaling pathways related to gastric precancerous lesions,including Pathways in cancer,HIF-1 signaling pathway,and NF-kappa B signaling pathway,TNF signaling pathway,Toll-like receptor signaling pathway,Bile secretion,PI3K-Akt signaling pathway,NOD-like signaling pathway,m TOR signaling pathway,VEGF signaling pathway,etc,among which there are 29 signaling pathways P<0.05.7 Drugs-active ingredient-target-pathway network: Cytoscape software is used to construct a drug-active ingredient-target-pathway network for the treatment of gastric precancerous lesions of Ecanjianwei Decoction.The network has a total of 153 nodes and 1101 edges,involving 14 drugs,37 active ingredients,73 potential targets,and 29 pathways.reflecting the characteristics of multi-component,multi-target and multi-channel mechanism of Ecanjianwei Decoction in treating precancerous lesions of gastric cancer.Conclusion:1 Through the query of Chinese medicine database,it is found that Ecanjianwei Decoction has a variety of active ingredients.Ecanjianwei Decoction treats gastric precancerous lesions because of its multiple active ingredients.15 kinds of active ingredients such as kaempferol,oxaxanthin,luteolin,baicalein,baicalin,etc.are the core active ingredients.2 Through the target prediction of Ecanjianwei Decoction for treating gastric precancerous lesions,it was found that the effective ingredients in the prescription can act on multiple targets of gastric precancerous lesions,IL6,AKT1,HSP90AA1,TNF,PTGS2,IL1 B,NFKB1,RXRA,PPARG,CEBPB and other 20 targets Point are the core target of Ecanjianwei Decoction in treating gastric precancerous lesions.3 Through the molecular docking verification of some core active ingredients and core targets of Ecanjianwei Decoction in the treatment of gastric precancerous lesions,it was found that kaempferol,acorns,luteolin,baicalein,baicalin and IL6,AKT1,HSP90AA1,TNF,and PTGS2 all have good binding activity.4 Through GO function enrichment analysis and KEGG pathway enrichment analysis,it is found that the potential targets of Ecanjianwei Decoction in the treatment of gastric precancerous lesions are mainly distributed in the nucleus,nucleus,cytoplasm,basolateral plasma membrane,and cytoplasm perinuclear area;Mainly involved in the regulation of the initial transcription of RNA polymerase II promoter,the positive regulation of nitric oxide biosynthesis process,the positive regulation of transcription from the RNA polymerase II promoter,etc;regulation of RNA polymerase II transcription factor activity,ligand Activated sequence-specific DNA binding,transcription factor binding,sequence-specific DNA binding and other functions;potential targets mainly involve Pathways in cancer,HIF-1 signaling pathway,NF-κB signaling pathway,TNF signaling pathway,Toll-like receptor signaling pathway,Bile secretion,PI3K-Akt signaling pathway,NOD-like receptor signaling pathway,m TOR signaling pathway,VEGF signaling pathway,and other signaling pathways.