The Law Of Medication And Network Pharmacology Analysis Of Traditional Chinese Medicine In The Treatment Of Hepatitis B Cirrhosis

Objective: To collect the relevant literature on the treatment of hepatitis B cirrhosis with traditional Chinese medicine(TCM)and explore the law of prescription medication by data mining(DM)technology,and screen core prescription drugs,so as to provide reference for the treatment of hepatitis B cirrhosis with TCM.To analyze the mechanism of core prescription drugs in the treatment of hepatitis B cirrhosis by the method of network pharmacology(NP),which provide the basis for further clinical and experimental research.Methods: 1 The literature of clinical research of TCM in the treatment of hepatitis B cirrhosis was searched on China National Knowledge Infrastruture(CNKI),Wan Fang Datebase,China Science and Technology Journal Database(VIP)and China Biomedical Literature Database(CBM)from the establishment of the batabase to December 31,2019.The retrieved literatures were screened according to the inclusion and exclusion criteria,and the prescriptions and TCM were collected.The frequency,four properties,five flavors,division of the meridians of the five zang-organs and efficacy of drugs were analyzed respectively by using traditional Chinese medicine inheritance computer system(TCMICS).The drug combinations and core prescription drugs were analyzed by association rules,and the core combinations were obtained by cluster analysis.2 The active ingredients of core prescription drugs were screened out by using TCMSP and TCMID database,and the related targets of active ingredients were obtained from TCMSP database.The targets of hepatitis B cirrhosis were obtained from Gene Cards database.The intersection targets of drugs and diseases were obtained and venn diagram was drawn on Draw Venn Diagram.The network of "TCM-active ingredients-targets-disease" was constructed by using Cytoscape,and the core active ingredients were screened out.The protein-protein interaction(PPI)network of intersection targets was obtained and core targets were analyzed on STRING and Cytoscape.The Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was carried out on DAVID.Results: 1 A total of 205 literatures were collected,from which 205 prescriptions of TCM in the treatment of hepatitis B cirrhosis were sorted out.The collected prescriptions were analyzed by using the TCMICS,and the following results were obtained:1)A total of 168 TCM were involved in the 205 prescriptions,of which the frequency of 31 TCM was ≥20 through frequency analysis.According to the order of frequency,the top 15 TCM were radix salviae,atractylodes macrocephala koidz,radix astragali,turtle shell,paeoniae radix alba,poria cocos,licorice,radix bupleuri,radix angelica sinensis,radix paeoniae rubra,persicae semen,curcumae radix,curcumae rhizoma,chuanxiong rhizoma and aurantii fructus.2)The medicinal properties were mainly cold,warm and flat.The five flavors of durgs were mainly bitter,sweet and pungent,the division of the meridians of the five zang-organs were mainly liver meridian and spleen meridian.The efficacy analysis found that TCM for tonifying deficiency,blood activating stasis removing drugs,heat-clearing drugs,diuretic dampness excreting drugs and qi regulating drugs were more used.3)A total of 20 drug combinations,18 drug combinations rules and 9 TCM were obtained by using association rule analysis,including radix salviae,atractylodes macrocephala koidz,radix astragali,turtle shell,paeoniae radix alba,poria cocos,licorice,radix bupleuri,radix angelica sinensis,and the 9 TCM were core prescription drugs.The first three common drug combinations of radix salviae and radix astragali,atractylodes macrocephala koidz and poria cocos,radix salviae and atractylodes macrocephala koidz.And the first 3 drug combinations rules were atractylodes macrocephala koidz,radix astragali and radix salviae,poria cocos and atractylodes macrocephala koidz,radix salviae,atractylodes macrocephala koidz and radix astragali.4)The 6 core combinations were obtained by cluster analysis,respectively as follow: the core combination 1 includes atractylodes macrocephala koidz,radix astragali,licorice,radix salviae,poria cocos,turtle shell and angelicae sinensis radix,core combination 2 includes radix paeoniae rubra,licorice,aurantii fructus,persicae semen,chuanxiong rhizoma,turtle shell,radix bupleuri and angelicae sinensis radixt,core combination 3 includes paeoniae radix alba,atractylodes macrocephala koidz,poria cocos,radix bupleuri,turtle shell,licorice,magnolia officinalis rehd et wils and aurantii fructus,core combination 4 includes angelicae sinensis radix,ophiopogon japonicus,radix rehmanniae,lycii fructus,turtle shell,toosendan fructus,radix salviae and adenophprae ae radix,core combination 5 includes turtle shell,radix astragali,radix salviae,curcumae rhizoma,angelicae sinensis radix,curcumae radix,atractylodes macrocephala koidz and paeoniae radix alba,core combination 6 includes paeoniae radix alba,radix astragali,radix salviae,atractylodes macrocephala koidz,poria cocos,radix bupleuri,lycopi herba and persicae semen.2 The core prescription drugs were obtained by association rules analysis,including radix salviae,atractylodes macrocephala koidz,radix astragali,turtle shell,paeoniae radix alba,poria cocos,licorice,radix bupleuri and radix angelica sinensis.And the mechanism of core prescription drugs in the treatment of hepatitis B cirrhosis was analyzed using NP,and the results were as follows:1)A total of 191 active components of core prescription drugs were obtained and213 intersection targets were screened out,of which 184 active components were corresponding to intersection targets.And 6 core active ingredients were screened out,including quercetin,kaempferol,luteolin,formononetin,naringenin and isorhamnetin.2)5 core targets were screened by PPI analysis,including AKT1,TP53,IL6,VEGFA and TNF.3)GO enrichment analysis showed that the intersection targets were mainly regulated 378 biological processes(BP)such as response to drug,response to ethanol and positive regulation of transcription from RNA polymerase II promoter,etc.The intersection targets were mainly distributed in 43 cellular component(CC),including extracellular space,cytosol,membrane raft and other cellular component,and mainly display 78 molecular functions(MF)such as enzyme binding,protein binding,protein homodimerization activity,etc.And KEGG pathway enrichment analysis showed that the intersection targets were significantly enriched in Hepatitis B,TNF signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,Fox O signaling pathway and other 108 pathways.Conclusion: 1 The treatment was mainly carried out from the liver and spleen.The drugs were selected according to the treatment principles of tonifying deficiency,promoting blood circulation and removing blood stasis,clearing heat and removing toxin,diuresis and dampness,soothing liver and regulating qi.2 The drug combinations were screened by association rules,including radix salviae and radix astragali,atractylodes macrocephala koidz and poria cocos,radix salviae and atractylodes macrocephala koidz,etc.The core combinations obtained by cluster analysis were added and subtracted on the basis of Xiaoyao Powder,Gexia Zhuyu Decoction,Chaihu Shugan Powder,Yiguan Jian,Rougan Sanjie Decoction,which provide ideas for clinical drug.3 The core prescription drugs were composed of radix salviae,atractylodes macrocephala koidz,radix astragali,turtle shell,paeoniae radix alba,poria cocos,licorice,radix bupleuri,radix angelica sinensis.The active components of core prescription drugs in the treatment of hepatitis B cirrhosis included quercetin,kaempferol,luteolin,formononetin,naringenin,isorhamnetin and other active components,which act on AKT1,TP53,IL6,VEGFA,TNF and other targets to regulate Hepatitis B,TNF signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,Fox O signaling pathway and other pathways to provide reference for further research.