Study On Medication Regularity And Mechanism Of Core Drug Pair Intreating Ulcerative Colitis With Warm Yang Method Based On Data Mining

Research objectives: 1.This study was conducted by comprehensively collecting the literature on modern warm-yang method for the treatment of ulcerative colitis in the database,applying association rules and clustering data mining methods,and conducting inductive analysis to derive the frequency of drug use and high-frequency use of the four qi,five tastes,and the attributive meridians of the corresponding herbal prescriptions,drug classes,grouping patterns and core drug pair combinations to provide theoretical guidance for clinical treatment.2.Based on the high-frequency core drug pair combinations obtained from the data mining results,the potential mechanism of action of the core drug pair combinations for the treatment of ulcerative colitis was investigated through network pharmacology to provide a theoretical basis for the future use of the drug combinations and further experimental studies.Research methods: 1.data mining analysis: all literature from Wanfang,Zhiwang,Wipu,and dissertation databases built up to January2022 were searched according to the search terms,and literature was screened according to the inclusion and exclusion criteria,and the corresponding Chinese medicine prescriptions were extracted from the literature that met the criteria.Excel 2019 was used to establish the original prescription database,enter the information of Chinese medicine prescriptions,and count the frequency of medication with the four qi,five tastes,attribution and efficacy categories of high frequency Chinese medicine.IBM SPSS Statistics 26.0 was used to cluster the high-frequency herbal medicines,and the Apriori algorithm in IBM SPSS Modeler 18.0 was selected for association rule analysis to mine out the high-frequency core drug combinations and explore the potential patterns among medication use,group prescriptions and ulcerative colitis.2.Network pharmacology analysis: This study will conduct a network pharmacology mechanism of action study based on the core drug pairs obtained by association rules and clustering analysis algorithms in data mining research.Swiss ADME,Swiss Target Prediction,Unitprot database and literature search supplement to obtain comprehensive information on the active compounds and their potential targets of the core drug pairs.Screening of UC disease-related target protein and target gene information in Dis Ge Net,TTD,OMIM and Drug Bank databases.The predicted targets of action of the core drug pair were mapped to the UC disease targets using the web platform Venny2.1 to extract the intersection targets.Using Cytoscape 3.9.1 software,a network diagram of "core drug pair-active ingredient-target-ulcerative colitis" was constructed.The PPI network was obtained by running the STRING database.After hiding the free nodes,the results were exported and then analyzed by the "Network Analyzer" function in Cytoscape 3.9.1 software to predict the core targets.The core drug pairs were imported into the DAVID 2021 database,and enrichment analyses were performed for gene ontology GO and Kyoto gene and Kyoto gene and genome encyclopedia KEGG pathway,respectively,to predict the potential mechanisms of action of the core drug pairs for the treatment of UC.Results:1.Medication rules of warming Yang therapy for ulcerative colitis based on data miningThe results of medication frequency in this study: 170 Chinese herbal prescriptions were obtained,involving 178 Chinese herbal medicines,with a total medication frequency of 1954 times.The top 24 herbs were selected as high-frequency drugs in descending order of frequency of use ≥1.0%,among which the top 10 were Bupleurum,Nutmeg,Radix et Rhizoma,Poria,Rhizoma Atractylodis Macrocephalae,Radix Ginger,Radix Paeoniae Alba,Radix Astragali,Cornu Cervi Pantotrichum and Glycyrrhiza glabra.The four qi in the high-frequency drugs are most often warm(464 times),followed by hot,flat,cold and cool.The five flavors were sweet(687times)the most,followed by pungent,bitter,sour,light,and astringent.The meridians are the spleen,stomach,lung,heart and kidney meridians,with the spleen meridian(1096 times)being the most frequent.The drug efficacy categories can be divided into 7 categories,among which 9 flavors(37.5%)are the most frequent for tonic deficiency,followed by4 flavors(16.67%)for warming the li and 4 flavors(16.67%)for collecting astringency.Results of high frequency drug cluster analysis: 6 clusters were obtained,which were: Ⅰ.Fructus officinalis-fructus schisandra-psoralea-nutmeg.Ⅱ Cinnamon-Chebula chebula-Paeoniae paeoniae-Woody Herb-Angelica sinensis;Ⅲ Astragalus-red stone fat;Ⅳ Aconite-Dried ginger-Coptis;Ⅴ Tangerine peel-Coix seed-Poria Coia-Atractylodes atractylodes codonopsis-Yam-sanguinis ulmus;Ⅵ Gun Ginger-Ginseng-Licorice.Association rule analysis results: 26 pairs of traditional Chinese medicine combinations,and psorale-nutmeg was the core pair with the highest support.The drugs used in the first 6 pairs of core drug combinations were psoralea psoralea,nutmeg,Wuzhuyu,Schisandra and aconite,which were mainly used as the main prescription of Sishen Pills.2.Network pharmacological study on the combination of psorale-nutmeg with core drug in the treatment of UC.A total of 43 active compounds were collected from the core drug pair of tonicin-myristica,with a total of 433 predicted targets of action.The main active ingredients for the treatment of UC were complement factor D-IN-1,tensin esterin I,8-(6-peroxy-3,7-dimethyl-2,7-octadienyloxy)psoralen,psoralen methyl,psoralenol,and psoralenin.The search of Dis Ge Ne,TTD,OMIM,Drugbank databases yielded 1522 UC disease-related targets and 125 drug-disease intersection targets.The PPI network results generated by STRING database platform were selected,and the core targets were AKT1,SRC,EGFR,MYC,etc.The results of GO functional enrichment analysis showed that the core drugs on biological processes were mainly manifested in protein phosphorylation,negative regulation of apoptotic process,inflammatory response etc.The molecular functions were mainly through binding to ATP,same protein binding,The results of KEGG pathway enrichment analysis,based on the P value(P ≤ 0.05),showed that the main effects of the core drug "Psoralen-Myristica" on the treatment of UC were related to the cancer pathways,lipids and atherosclerosis,prostate cancer,hepatitis B,etc.Conclusion.1.Based on the literature data mining method to analyze the prescription medication pattern of TCM warming method for UC,it was concluded that the medication is mainly based on warming the spleen and tonifying the kidney,cultivating the earth and building up the middle,with Si Shen Wan as the base usage for addition and subtraction,and the commonly used core medication pair is tonic-syringomyelia.At the same time,it is also concluded that the therapeutic use will be focused according to the different development of the disease of UC,from the overall development of the appropriate complementary other methods,the combination of drugs also reflects this,warming and tonifying and clearing,supporting the righteousness and eliminating evil,such as warming the spleen and tonifying the kidney,warming the Yang to clear heat and dampness,warming the Yang to remove the liver and strengthen the spleen.2.By the method of network pharmacology analysis,it was predicted that the main active ingredients of the core drug of psoralen-myristica for the treatment of UC were mainly through the com-plement factor D-IN-1,tensin esterin I,8-(6-peroxy-3,7-dimethyl-2,7-octadienyloxy)psoralen,psoralen methyl,psoralenol,psoralenin and other major active ingredients acting on key targets such as AKT1,SRC,EGFR,MYCetc.which are involved in anti-inflammatory,anti-tumor,regulation of cell proliferation and apoptosis,antioxidant and other stress responses,regulation of immune response and intestinal flora to achieve the effect of UC treatment.