Investigating The Mechanism Of Yueju Pills In Treating Functional Dyspepsia Based On Network Pharmacology

Objective: To use the method of network pharmacology to construct a biological network of Yueju pills’ components-targets-functional dyspepsia,and to explore the mechanism of Yueju pills’ treatment of functional dyspepsia through the analysis of the network.Methods: The TCMSP database and the relevant literature in CNKI were used to retrieve the chemical components and the targets of the chemical components in Yueju Pills;the Gene Cards database were used to retrieve the disease targets involved in functional dyspepsia,and the Relevance score<20 targets were removed;the names of all targets were standardized in the Uniprot database;the Venny 2.1.0 were used to draw the Venn diagram of the targets related to the chemical composition of Yueju pills and the targets related to functional dyspepsia,and obtain the function of Yueju pills targets of functional dyspepsia;Cytoscape were used to construct the biological network of Yueju pills’ components-targets-functional dyspepsia,and the key chemical components and core targets of Yueju pills for the treatment of functional dyspepsia were determined by topological analysis;the Bio GPS database were used to locate the core targets,draw and analyze the core targets-tissues distribution network;the Ledock were used to molecularly dock the key chemical components and positive drugs with the core targets,and verify the composition of Yueju pills through the binding ability;GO biological process and KEGG signal pathway enrichment analysis on the target of Yueju pills in the treatment of functional dyspepsia through DAVID database,to determine the biological nature of Yueju pills in the treatment of functional dyspepsia process and signal pathways to explore the mechanism of action of Yueju Pills in treating functional dyspepsia.Results:(1)The chemical components and targets of Yueju Pills: A total of 434 chemical components and 554 targets of Yueju Pills were collected through the TCMSP database and literature;(2)Disease targets and intersection targets for functional dyspepsia: Obtain functional dyspepsia-related targets from the Gene Cards database.A total of 2,452 targets were retrieved.After screening,89 targets with Relevance score ≥ 20 were obtained,of which 35 targets that overlap with the targets of Yueju pills;(3)Yueju pills’ components-targets-functional dyspepsia biological network: The Cytoscape 3.7.2 were used to draw Yueju pills component-target-functional dyspepsia biological network,including 112 nodes and 216 edges.Topological structure analysis is carried out through the Network Analyzer plug-in.At the same time,18 key network nodes satisfying the arithmetic mean of Degree value,BC value and CC value,contain 3 key chemical components(quercetin,methyl 2-pentanoyl benzoate,Paeonol)and 15 core targets(SLC6A3,ESR1,HTR2 A,TNF,PPARG,IL6,REN,TP53,CCND1,AKT1,SOD1,IL1 B,CAT,IL10,PTEN);(4)Tissue distribution: The 15 core targets of Yueju Pills for the treatment of functional dyspepsia are mainly expressed in 59 human body tissues,including brain tissue,nerve tissue,muscle tissue,liver,kidney,ovary,adipose tissue,blood,and lymph.cells,etc.,among which16 tissues are co-expressed by multiple targets,reflecting the synergy between the targets;(5)Molecular docking: The binding rate of the key chemical components to the core targets is 100%,16% of the docking results are less than or equal to-5kcal/mol,and 12% of the docking results are less than the positive drug docking results,indicating that the key chemical components and the key targets have strong binding power;(6)Enrichment analysis: The DAVID database were used to perform the GO and KEGG enrichment analysis of key targets,and enter the 35 intersection targets information of Yueju pills into the database,and the species is selected as "Homo sapiens",and a total of p<0.05,FDR is obtained <0.05,Count>5 conditions of 24 GO biological processes and 38 KEGG signal pathways.GO biological processes include positive regulation of RNA polymerase II promoter transcription,response to drugs,negative regulation of aging,apoptosis process,positive regulation of transcription,DNA template,inflammatory response,positive regulation of nitric oxide biosynthesis,immunity reaction,etc.;KEGG signaling pathways include cancer pathway,Fox O signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,inflammatory bowel disease(IBD),cytokine and cytokine receptor interaction,Jak-STAT signaling pathway,HIF-1 signal pathway,etc.Conclusion:The mechanism of Yueju Pills in treating functional dyspepsia may be:(1)Regulate the cell cycle by regulating the expression of genetic material,play the role of anti-inflammatory,anti-oxidant,and protect the gastric mucosa,increase the pain threshold,relieve the hypersensitivity of the internal organs,and reduce the pain and burning sensation of the gastric cavity;(2)Regulate nerve conduction,correct brain-gut axis disorders,regulate the secretion of insulin,bile,gastric acid,and small intestinal fluid,and promote the proliferation of vascular endothelial cells,thereby promoting the metabolism of the three major nutrients,reducing postprandial discomfort and fullness;(3)Regulate smooth muscle function and enhance gastrointestinal motility to improve symptoms of anorexia;(4)Regulate autonomic disorders,reduce heart rate,soothe emotions,so as to regulate emotions and vitality;(5)Regulate the balance of the gastrointestinal flora.