| Objective:To screen the main active ingredients of Guben Tongluo Decoction in treating chronic atrophic gastritis,predict the target of its active ingredients,establish drug-component-target-disease network,and explore the mechanism of Guben Tongluo Decoction for the treatment of chronic atrophic gastritis.Method:The potential active ingredients of Guben Tongluo Decoction were screened by pharmacokinetic parameters OB and DL in TCMSP,and the therapeutic targets of Guben Tongluo Decoction for chronic atrophic gastritis were predicted and screened by integrating STPD,Gene card and OMIM.With the help of Cytoscape,a drug-component-target-disease network is constructed.The protein interaction network was drawn by String database and Cytoscape software,and the type of target was assigned by DisGeNET database.The biological function and metabolic pathway of Guben Tongluo Decoction were analyzed by DAVID database.Result:(1)A total of 2354 active ingredients of 21 components of Guben Tongluo Decoction were retrieved from the database.There 407 active ingredients were screened according to "OB>30%and DL>0.18".339 active ingredients were obtained by removing common active ingredients of drugs.Among them,134 active ingredients of Codonopsis pilosula and 21 potential active ingredients were screened,34 active ingredients of Poria cocos were screened.Fifteen potential active ingredients were obtained;55 active ingredients of Atractylodes macrocephala and 7 potential active ingredients were obtained through screening;116 active ingredients of Pinellia temata and 13 potential active ingredients were obtained through screening;349 active ingredients of Bupleurum chinense and 17 potential active ingredients were obtained through screening;104 active ingredients of Rhizoma Cyperi and 18 potential active ingredients of Paeonia lactiflora were obtained through screening.A total of 85 active ingredients were screened and 13 potential active ingredients were obtained;57 active ingredients of Pinus kansuensis and 5 potential active ingredients were screened;81 active ingredients of Curcuma zedoaria and 3 potential active ingredients were screened out;202 active ingredients of Salvia miltiorrhiza were screened and 65 potential active ingredients were obtained;38 active ingredients of Coix seed were screened and 9 potential active ingredients were obtained.There were 280 potential active ingredients of liquorice,92 active ingredients were obtained by screening;165 potential active ingredients of Amomum villosum,10 active ingredients were obtained by screening;40 potential active ingredients of Wumei,8 active ingredients were obtained by screening;78 potential active ingredients of Curcula villosa,7 active ingredients were obtained by screening;and the potential active ingredients of Epimedium vulgaris were obtained by screening.A total of 130 active ingredients were screened and 23 active ingredients were obtained;114 potential active ingredients of Cnidium mongolicum were screened and 19 active ingredients were obtained;31 potential active ingredients were screened and 8 active ingredients were obtained;46 potential active ingredients of Morus parasitism were screened and 2 active ingredients were obtained;140 potential active ingredients of Phellodendron amurense were screened and 37 active ingredients were obtained.There were 75 potential active ingredients in Anemarrhena asphodeloides,and 15 active ingredients were obtained by screening.(2)A total of 542 drug targets were obtained in this study,including 149 potential targets of Codonopsis pilosula,67 potential targets of Poria cocos,53 potential targets of Atractylodes macrocephala,124 potential targets of Pinellia ternata,120 potential targets of Bupleurum,167 potential targets of incense,98 potential targets of Paeonia lactiflora,57 potential targets of Gansong and 3 potential targets of Zedoary turmeric.There were 216 potential targets for Salvia miltiorrhiza,45 potential targets for Coix seed,211 potential targets for licorice,56 potential targets for Amomum,61 potential targets for Cinnamomum,37 potential targets for Cinnamomum,121 potential targets for Epimedium,100 potential targets for Cnidium,and 70 potential targets intermittently.There are 30 potential targets for mulberry parasitism,161 potential targets for Phellodendron amurense and 124 potential targets for Anemarrhena asphodeloides.(3)This study found that the interaction network between Guben Tongluo Decoction and CAG involved 973 nodes,edges:2739,P<0.01.The network topological relationship was obtained by Cytoscape software analysis function.The median of "degree","closeness" and "betweenness" were the card values.In this paper,the degree was 112,and the closeness was 0.49.767,betweenness was 0.002008.69 key nodes of CAG disease target interaction network were selected as potential targets of Guben Tongluo Decoction.Among them,AKT1,IL6,ALB,TP53,TNF,VEGFA,EGFR,CXCL8,STAT3,EGF,MAPK1,SRC,CASP3,IL10,MAPK8,JUN,PTGS2,MMP9,ESR1,IL1B were higher than 230,P<0.05.(4)The main biological processes of target proteins were determined by GO-BP analysis.By GO-BP analysis,211 biological process information were obtained from the core target,and 201 biological process information with significant significance(P<0.01).Thirteen biological process information were obtained,such as table 66,from which the number of genes(>20)was screened.Biological processes are classified into signal transduction,redox,RNA polymerase regulation,cell proliferation and apoptosis regulation,inflammatory response,protein hydrolysis,gene expression regulation,protein phosphorylation.(5)A total of 177 gene pathways related to the target of Guben Tongluo Decoction were enriched by KEGG analysis.There were 147 gene pathways with significant significance(P<0.01).43 chronic atrophic gastritis related pathways were obtained by removing other disease pathways from the pathway information.Pathways in cancer,PI3K-Akt signaling pathway,TNF signaling pathway,MAPK signaling pathway,Rapl signaling pathway,FoxO signaling pathway,Toll-like receptor signaling pathway,HIF-1 signaling pathway have higher number of input,which are 36,26,18,16,16,16,16,16,16 respectively.The target points involved are 397,342,110,255,211,134,106,103 respectively..Conclusion:(1)By searching the database,we found that Guben Tongluo Decoction has many kinds of compounds,and Guben Tongluo Decoction has many kinds of active ingredients in treating chronic atrophic gastritis.Stigmasterol,quercetin,kaempferol,sitosterol,beta-sitosterol,isorhamnetin and Mairin may be the core compounds of Guben Tongluo Decoction in treating chronic atrophic gastritis.(2)It was found that the active ingredients of Guben Tongluo Decoction could act on multiple targets through target prediction and screening of active ingredients.Guben Tongluo Decoction mainly through transcription factors,enzymes,transporters,Membrane receptors,tyrosine kinase(Tyr Kinase),serine-threonine kinase(Ser Thr kinase)Tyr Phosphatase,Serine Protease,Ion Channel,Aspartic Protease and Cysteine Protease play therapeutic roles.(3)Through the interaction of component-target-disease network,it can be found that the active ingredients of Guben Tongluo Decoction are related to multiple target proteins and pathways,and that the prescription is strongly related to a few important targets in the treatment of CAG.It was found that the targets of AKT1,IL6,ALB,TP53,TNF,VEGFA,EGFR,CXCL8,STAT3,EGF,MAPK1,SRC,CASP3,IL10,MAPK8,JUN,PTGS2,MMP9,ESR1,IL1B were closely related to the active ingredients of Guben Tongluo Decoction and chronic atrophic gastritis.(4)Through GO analysis,it was found that Guben Tongluo Decoction plays a biological role mainly by regulating signal transduction,redox,RNA polymerase regulation,cell proliferation and apoptosis regulation,inflammatory response,protein hydrolysis,gene expression regulation,protein phosphorylation and other processes.(5)Through KEGG pathway analysis,it was found that Guben Tongluo Decoction could treat chronic atrophic gastritis mainly by interfering with Pathways in cancer,PI3K-Akt signaling pathway,TNF signaling pathway,MAPK signaling pathway,Rapl signaling pathway,FoxO signaling pathway,Toll-like receptor signaling pathway and HIF-1 signaling pathway. |
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