Exploring The Mechanism Of Action And Molecular Docking Validation Of Zhizhu Kuanzhong Capsule For Treating Functional Dyspepsia Based On Network Pharmacology

Objective:Zhizhu Kuanzhong capsule in the long-term clinical application of functional Dyspepsia(FD)has achieved satisfactory results,but the Chinese medicine itself has many components,mechanism of action,and the interaction between each other is not clear,this paper uses network pharmacology theory,the four kinds of traditional Chinese medicines of Zhizhu Kuanzhong capsule baishu,citrus fruit,chaihu,hawthorn have been carried out in depth,in order to provide a new basis and research direction for the specific mechanism of action of Zhizhu Kuanzhong capsule treatment FD.Methods:Based on the Chinese Medicine System Pharmacology Database(TCMSP)and consulting the relevant literature to obtain the relevant chemical components of the four Chinese herbal medicines of Zhizhu Kuanzhong capsules,the activities of the chemical ingredients were screened by using the Swiss ADME website,and the potential targets of the active chemical ingredients were searched in the Swiss Target Prediction for the ingredients that met the requirements,and the FD disease targets were retrieved through gene Cards and OMIM databases.Further use the Wayne diagram to map and screen out the common targets of diseases and drugs,that is,the potential targets for the treatment of FD in citrus aurantium wide capsules;use Cytoscape Version 3.7.2 software to map "drug-active ingredient-target network" and "drug-disease-target network" to screen out the core active ingredients;use string database to map and build protein protein interaction network(PPI)Analyze the interactions between these common targets to identify potentially key genes;utilize the R software in "org.Hs.eg.db" and "Clusterprofiler" R packages were analyzed by Gene Ontology(GO)and enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes(KEGG),and the mechanism of action of Zhizhu Kuanzhong capsules in the treatment of FD was preliminarily analyzed The core active ingredient and key target protein of the citrus aurantium wide capsule were verified by using Auto Dock and Pymol.Results:Obtained a total of 60 active ingredients of Zhizhu Kuanzhong capsule,6 baishu,22 citrus fruits,17 chai hu,16 hawthorns,and a total of 60 active active ingredients for deduplication,and 954 active target genes were obtained.659 FD disease-related targets were obtained,and 179 potential targets for the treatment of FD by Zhizhu Kuanzhong Capsule were obtained after Venn analysis.Through the analysis of the visual network related to the treatment of FD in Zhizhu Kuanzhong capsule,it was obtained that the possible core components of the treatment of FD in citrus aurantium kuanzhong were Isosinensetin and 14-acetyl-12-senecioyl-2E,8Z,10E-atractylentriol,5,7,4’-Trimethylapigenin,Troxerutin,Nobiletin,etc.Analysis of PPI networks can obtain SRC,HSP90AA1,TP53,STAT3,MAPK3,AKT1,EGFR,HRAS,MAPK1,VEGFA as the core targets.The analysis screened 3349,and the target gene was enriched in biological processes(BP)with 2963,mainly focusing on the positive regulation of protein serine/threonine kinase activity and peptidyl-tyrosine phosphoryl phosphorylation),peptidyl-tyrosine modification,etc.;there are 133 cell components(CC),mainly concentrated in membrane raft,membrane microdomain,membrane region,membrane region,Glutamatergic synapse(glutamatergic synapse),vesicle lumen,etc.;molecular function(Molecular Function,MF)has 253,mainly focusing on protein tyrosine kinase activity,transmembrane receptor activity(transmembrane receptor protein tyrosine kinase activity)and others.KEGG pathway enrichment analysis showed that the target genes were mainly enriched in PI3K-Akt signaling pathway,Ras signaling pathway,Rap1 signaling pathway,etc.Molecular docking showed that the core active ingredients in the screening of citrus aurantium wide had good binding activity with their corresponding target proteins.Conclusion:The study screened the active ingredients and FD disease-related targets of Zhizhu Kuanzhong capsules by network pharmacology and molecular docking technology,and analyzed and elaborated the core active ingredients,core targets and related pathways of Zhizhu Kuanzhong for the treatment of FD.The core active ingredient in the treatment of FD in citrus aurantium is Isosinensetin,14-acetyl-12-senecioyl-2E,8Z,10E-atractylentriol,and 5,7,4’-Trimethylapigenin,Troxerutin,Nobiletin,Sweet Orange Flavonoids Sinensetin,Petunidin,Caffeic acid,Sexangularetin,Eriodyctiol flavanone.These components are predicted in this study to play a role in treating FD by targets such as SRC,HSP90AA1,TP53,STAT3,AND MAPK3 by adjusting channels such as PI3K-Akt signal pathway,Ras signal pathway,and Rap1 signal pathway.Molecular docking shows that the study predicts that the core active ingredient has good binding activity to the core target protein.The treatment of FD with Zhizhu Kuanzhong capsule is the result of the joint action of multiple active ingredients,multiple action targets,and multiple regulatory pathways,and this study excavates the biological processes,places,signaling pathways,etc.in the treatment process in order to have a preliminary prediction of its mechanism of action.However,this study is subject to the inevitable lack of information in the database,and in order to obtain more accurate results,it is necessary to consider verifying the prediction results through further animal experiments.