Research On Medication Rule And Action Mechanism Of Traditional Chinese Medicine In The Treatment Of ITP Using The Data Mining And Network Pharmacology

Objective: Searching on the computer about the published literature of traditional Chinese medicine in the treatment of primary thrombocytopenic purpura(ITP)in 7 databases at home and abroad,mining the medication rules of them,and analyzing its mechanism and potential targets.In order to further provide certain reference for the drug research and development,experimental research and clinical application of traditional Chinese medicine in the treatment of ITP.Methods: 1.Searching on the computer on CNKI,Wanfang Data,VIP,CBM,Pub Med,Cochrane Library and Web Science,the retrieval period is from January 2000 to April 2022.Collecting and screen the relevant literature of the clinical cases that was treated by TCM about ITP,then built the TCM prescription database.and import the TCM data information into Excel 2019.SPSS Modeler 18.0 and SPSS Statistics22.0 were used as statistical analysis tools to carry out frequency statistics,association rules,complex network analysis and cluster analysis.Discuss the treatment principles and methods,drug matching and prescription rules,and extract its core drug combination.2.The effective components of core drugs were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database.If the drug components cannot be retrieved in TCMSP,the chemical structural formula of the components can be obtained through the chemical component database query and literature search and supplement.The chemical structural formula of the components can be entered into the Swiss ADME platform to screen the effective components that meet the requirements.Finally,all the effective components of the drug are entered into the Swiss Target Prediction platform to predict the potential target of the compound.The target of ITP is obtained through Gene Cards database,Drug Bank database,OMIM database,Dis Ge NET database,Dig See database and TTD database.Build a potential target-component network diagram through Cytascape 3.8.0and conduct topology analysis to obtain core components.Enter the intersection target of drug targets and disease targets into STRING 11.5platform to build core protein PPI network,import the results into Cytascape 3.8.0 software to visualize the results,and obtain the core target through network topology analysis.Use Metascape platform to conduct GO function enrichment and KEGG analysis on intersection target.Results: 1.A total of 184 articles were included in this study,and184 Chinese herbal prescriptions were obtained,involving 210 Chinese herbal medicines.The total frequency of drugs use was 2118 times,among which the top 6 were Angelica Sinensis Radix,Agrimonia Eupatoria,Hedysarum Multijugum Maxim,Radix Rehmanniae,licorice and Cortex Moutan.The first five categories of drugs are qi-invigorating herbs,heat clearing and blood cooling drugs,blood tonic drugs,yin tonic drugs and astringent hemostatic drugs.The Four Properties of traditional Chinese medicine are mainly composed of mild drugs,mild drugs and cold drugs.The Five Tastes of traditional Chinese medicine are mainly sweet,bitter and pungent.The Channel-tropism of drugs are Liver Meridians,Heart Meridians,Spleen Meridians and Kidney Meridians.The drug combination with the highest support in the analysis of the association rules of two traditional Chinese medicines are:Radix Rehmanniae and Cortex Moutan.The association rules of three traditional Chinese medicines are: Radix Rehmanniae and Cortex Moutan-Agrimonia Eupatoria.Four prescriptions were collected by systematic cluster analysis.The first category is Ecliptae Herba,Fructus Ligustri Lucidi,and Paeoniae Radix Alba,which are flavored with Erzhi Wan.The second category is Radix Rehmanniae,Cortex Moutan,Radix Paeoniae Rubra,buffalo horn,licorice,Rubia Cordifolia,Lithospermum Erythrorhizon,Spatholobus Suberectus Dunn,Hedysarum Multijugum Maxim and Imperatae Rhizoma,which are Modification of Rhinoceros Horn and Rehmannia Decoction.The third category is Atractylodes Macrocephala Koidz,prepared licorice,poria cocos,prepared Hedysarum Multijugum Maxim,Codonopsis Radix and Angelica Sinensis Radix,which are added or subtracted from Sijunzi Decoction.The fourth category is donkey-hide gelatin,Rehmanniae Radix Praeparata,Radix Salviae and Lycii Fructus,which are new prescription obtained by systematic clustering.According to the results of high-frequency drugs,association rule analysis and systematic cluster analysis,the core drug combinations for the treatment of ITP were determined as Angelica Sinensis Radix,Agrimonia Eupatoria,Hedysarum Multijugum Maxim,Radix Rehmanniae and Cortex Moutan.2.33 effective components and 306 drug component targets were obtained in totally after combined and removed the repeat of all drug effective components.1517 disease targets were actually collected from2367 disease targets.72 targets were finally obtained from drug component targets and disease intersection targets.At the potential action target-component network diagram,five key components in the top 5degree value were screened,including kaempferol,quercetin,β-Sitosterol,mairin,luteolin.17 core targets were screened in PPI network eventually,including AKT1,VEGFA,SRC,EGFR,CASP3,etc.The GO function enrichment analysis included 1203 biological processes,including positive regulation of protein phosphorylation,transmembrane receptor protein tyrosine kinase signaling pathway,enzyme-linked receptor protein signaling pathway,positive regulation of cell migration and positive regulation of cell motility,etc.There are 78 cellular components,including membrane raft,membrane microdomain,receptor complex,cell body and neuronal cell body,etc.There are 95 molecular functions,including protein tyrosine kinase activity,protein kinase activity,phosphotransferase activity,alcohol group as acceptor,kinase activity and transmembrane receptor protein tyrosine kinase activity,etc.There are145 KEGG pathways which related to ITP are PI3K-Akt signaling pathway,Micro RNAs in cancer and MAPK signaling pathway,etc.Conclusions: 1.Based on the method of data mining,it can be concluded that the most common type of drugs used for the treatment of ITP is the tonic type,which is supplemented by clearing heat and cooling blood,astringent hemostasis,etc.It is suggested that the prescription should be used on the basis of syndrome differentiation and treatment,and the treatment should be achieved by regulating cold and heat evenly,mainly by tonifying and clearing,tonifying Qi and Yin to stop bleeding,enrich the blood to stop bleeding,clearing heat and cooling blood to stop bleeding,etc.2.Based on the network pharmacology,the author preliminarily discussed the mechanism of core drug combination(Angelica Sinensis Radix,Agrimonia Eupatoria,Hedysarum Multijugum Maxim,Radix Rehmanniae and Cortex Moutan)in the treatment of ITP.It was predicted that the core drug combination might act on multiple targets such as AKT1,VEGFA,SRC and other targets through various components such as naphthol,quercetin,β-sitosterol and so on,participate in the PI3K-Akt signaling pathway,Micro RNAs in cancer and MAPK signaling pathway ect,to play a pharmacological role in anti-inflammatory,immune regulation,regulation of cell growth and differentiation,oxidative stress and other pharmacological effects,thereby playing a therapeutic role in ITP.