Mining And Mechanism Research Of Core Recipes For Diarrhea-type Diabetic Enteropathy Based On Network Pharmacology

Purpose:Apply data mining and network pharmacology research methods to study the rules of traditional Chinese medicine in the treatment of diarrheal diabetic enteropathy,explore common drug pairs and basic prescriptions for the treatment of diarrheal diabetic enteropathy,and explore the rules of drug use in the treatment of this disease.Simultaneously predict the active ingredients,targets and signal pathways of Sishen Pills in the treatment of diarrheal diabetic enteropathy,construct a biomolecular network,and explore its role in the treatment of diarrheal diabetic enteropathy from multiple levels and perspectives of "drug-component-target-pathway" Mechanism to provide certain information and data support and reference basis for new drug development and research.Material and method:1.Search the literature on the treatment of diarrheal diabetic enteropathy by oral Chinese medicine in Chinese databases such as CNKI,Weipu,Wanfang,etc.The literature was screened according to the inclusion criteria and the discharge criteria,and the data extracted were used to establish a database for the treatment of diarrheal diabetic enteropathy with traditional Chinese medicine prescriptions.Use Excel 2010 software to analyze the frequency of medicines,medicines,medicine properties,medicine tastes,and meridians.SPSS Modeler18.0 software performs association analysis;SPSS Statistics 22.0 software performs R-type clustering.Discuss the rule of medication for diarrheal diabetic enteropathy.2.Use TCMSP and BATMAN-TCM databases to retrieve the chemical components of Sishen pills,predict protein target information,and establish a database of active ingredients of Sishen pills—targets.Search for potential targets of diarrheal diabetic enteropathy in Gene Cards,DRUGBANK,TTD,and Disgenet databases.Take the intersection of drug targets and disease targets and import them into STRING11.0 database to construct a protein interaction(PPI)network.And use the MCODE plug-in of Cytoscape software to construct the molecular interaction module in the PPI network,and use Network analysis and the plug-in Cyto NAC to screen key targets.The intersection gene targets were imported into the Metascape database to conduct GO enrichment and KEGG pathway enrichment analysis on the targets.Finally,the "Sishen Pill active ingredient-target-pathway" network diagram was constructed by Cyto Scape 3.7.1 software.Results:1.The rule of medication for diarrheal diabetic enteropathy shows that commonly used high-frequency Chinese medicines include Atractylodes macrocephala,Codonopsis,Astragalus,Chinese Yam,Poria,Psoralen and Nutmeg.The most commonly used medicines are qi-tonifying drugs,and the warm,sweet and spleen-stomach meridians are often common in nature and flavor.Association rules: psoralen and nutmeg have the highest confidence of78.57%,followed by yam and astragalus 77.03%.Clustering prescriptions:(1): Psoralen,nutmeg,myrobalan,schisandra,evodia,ebony,are additions and subtractions from Sishen pills;(2): cohosh,bupleurum,astragalus,yam,atractylodes,codonopsis,coix seed,white lentils,Amomum,dried tangerine peel,Poria,lotus seeds,are the addition and subtraction of Shenling Baizhu San;(3): Aconite,dried ginger,dogwood,licorice,kudzu root,atractylodes,ginseng,salvia,coptis,scutellaria,white peony,cinnamon,angelica,woody,It is the addition and subtraction of Shaoyao Decoction.2.Sishen pills have 70 active ingredients and 463 targets,psoralen has 274 targets,nutmeg has 66 targets,evodia has 201 targets,schisandra has 20 targets,and ginger has 54 targets.There is one target,and there is one target in jujube 204.Obtained 566 disease targets.From the Venn diagram,there are 120 co-target genes for Sishen pills and diarrheal diabetic enteropathy.After module analysis of the target,three modules are mainly enriched,which are mainly related to adrenergic receptor activity,insulin-like growth factor receptor activity,adenosine phosphate kinase signaling pathway and G protein-coupled receptor signaling pathway.A total of 19 main target information was obtained: TNF,AKT1,JUN,IL6,VEGFA,TP53,MAPK1,INS,CXCL8,EGFR,MAPK14,EGF,EDN1,FOS,CTNNB1,IGF1,IL1 B,F2,ALB.The results of GO enrichment and KEGG pathway enrichment show that the protein genes regulated by Sishen pills are mainly enriched in response to lipopolysaccharide,adrenergic receptor activity,insulin-like growth factor,AGE-RAGE signaling pathway,and hypoxia-inducible factor-1 signal pathway,c GMP-PKG signal pathway,NF-?B signal pathway,adenosine monophosphate activated protein kinase signal pathway and other signal pathways.The active ingredient-target-pathway diagram of Sishen Pill involves 14 active ingredients,89 gene targets,and 20 pathways.The top 8 active ingredients of traditional Chinese medicine are quercetin,bakuchiol,isopsoralen,phytosterol,?-sitosterol,isoguaiacol,evodia,and isopsoralen.Conclusion:1.The medication rules for diarrheal diabetic enteropathy mostly involve traditional Chinese medicines that are sweet and warm to invigorate deficiency,replenishing qi and invigorating the spleen,and menstruation is also related to the spleen,stomach,and kidneys.It can be inferred that the clinical syndromes are mostly yang-qi deficiency and spleen-qi weakness.The clustering prescription Sishen Pill and Shenlingbaizhu Powder also confirm this point.In addition,it also involves the gastrointestinal damp-heat syndrome.Peony decoction is often used.Reduce treatment.2.This study uses the network pharmacology analysis method to reveal the active ingredients,gene targets and signal pathways of Sishen Pill on diarrheal diabetic enteropathy at the system level.It is preliminarily explained that the therapeutic effect of Sishen Pill on diarrheal diabetic enteropathy may be through regulating anti-oxidative stress,inhibiting the release of inflammatory factors,cytokines and hormones,regulating gastrointestinal tissue structure,remodeling biomechanical properties and gastrointestinal motility function And so on.