Exploring The Medication Rules And Mechanism Of Action Of Traditional Chinese Medicine In The Treatment Of Non-alcoholic Fatty Liver Disease Based On Literature Data Mining And Network Pharmacolog

Objective:Data mining of traditional Chinese medicine prescriptions for the treatment of nonalcoholic fatty liver disease(NAFLD)in the database is carried out.By using data mining techniques such as frequency analysis,cluster analysis and association rule analysis,High-frequency drugs,medication characteri stics and prescription rules for NAFLD were analyzed,core drug combinations for NAFLD were explored,effective components of core drug groups were analyzed by network pharmacology,and potential targets and signaling pathways were predicted to explore the mechanism of action for NAFLD.To provide theoretical support for the clinical application of TCM in the treatment of NAFLD.Methods:Search China national knowledge internet(CNKI),China Science and Technology Journal Database(VIP Database)and Wanfang Patent Database(WFPD)all literatures on TCM treatment of NAFLD from the establishment of the database to January 1,2022,were screened out according to the Nadp standard.Exce12010 was used to calculate and analyze the distribution of high frequency traditional Chinese medicine,sex and flavor normalization,efficacy and so on in literature.SPSS statistics 25.0 was used for cluster analysis to explore the formula rules of traditional Chinese medicine,and SPSS Modeler 18.0 was used for drug association rule analysis to get the core drug combination.TCMSP database was used to screen the active ingredients of the Drug group,and target prediction of the screened active ingredients was performed in the Drug Bank database.Target information of NAFLD was retrieved by OMIM database and Gene Cards database,and all target information was standardized by Uniprot database.The compose-target intersection genes were input into the DAVID database for GO functional enrichment and KEGG pathway enrichment analysis to explore the potential mechanism of action of drug groups in the treatment of NAFLD.The intersection genes were imported into STRING database to generate protein interaction network map,and the core targets were screened out.Cy toscape software is used to visualize the relationships among diseases,pathways,targets,Chinese medicines,active ingredients and protein interactions.Results:1.Frequency analysis of traditional Chinese medicine:A total of 453 traditional Chinese medicine prescriptions were screened in this study,including 226 prescriptions with syndrome differentiation.All prescriptions involved 222 kinds of traditional Chinese medicine,with a total of 4798 times of use of traditional Chinese medicine.Overall drug distribution results showed that hawthorn,alisma alisma,poria cocos,Danshen,Bupleurum,Atractylodes,cassia seed,glycyrrhiza,Turcyrrhizae,Tangerine peel,Pinellia pectoralis,Radix paeoniae alba,Radix Polygonatum,Radix Radix Astragalus,rhubarb,Polygonum multiflorum,Radix Paeoniae alba,Coix seed,Polygonum cuspidate,Radix angelica,Radix Coix,Fructus aurantii and atractylodes were the most commonly used medicines in the treatment of NAFLD.In the analysis of sex and flavor normalization,cold(38.7%),warm(31.9%)and flat(22.5%)were the most commonly used drugs of four Qi,followed by cool(5.4%)and hot(1.3%).The distribution of five tastes was as follows:sweet(30.5%)>bitter(29.9%)>octyl(22.4%)>salty(6.4%)>sour(4.9%)>light(3.2%)>astringent(2.6%);The top four drugs were liver(21.1%),lung(14.3%),stomach(14.2%)and spleen(14.0%).In the distribution of drug efficacy,the occurrence frequency of tonifying deficiency drugs was the highest,followed by tonifying water and dampness,promoting blood circulation and removing blood stasis,clearing heat,relieving food and regulating qi.The use frequency of tonifying qi and tonifying blood was the highest.Th e use frequency of tonifying water and dampness was the highest.2.Cluster analysis:Four drug combinations were obtained by sys tematic cluster analysis of 24 kinds of high frequency Chinese me dicines,and one was clustered:Tangerine peel-pinellia pinellia-Po ria coco-Atractyloides codonopsis-Bupleurum radix-Radix paeoniae alba-Glycyrrhiza alba-Radix angelica angelica;Cluster of two type s:Hawthorn-cassia seed-Salviorrhiza miltiorrhiza-Polygonum mul tiflorum-alisma alisma-Rhubarb-Fructus aurantii;Poly three ca tegories:wormwood-Polygonum cuspidatum-Astragalus-Coix-atract ylodes;Cluster four groups:lotus leaves.3.Analysis of associati on rules:Among the association rules prescribed in literature,the re are 5 association rules of two and 27 association rules of thre e,among which hawthorn,Salviorrhiza and Purpura purpura have t he highest support degree and high confidence degree,40.1%and 83.5,respectively.Hawthorn-cassia seed,Hawthorn-Salviorrhizaalisma alisma are important combinations in the treatment of NAF LD.4.Network pharmacological analysis:According to the data m ining results,Hawthorn,salvia miltiorrhiza and alisma alisma wer e selected as the core drug combination for network pharmacologi cal analysis.Quercetin,luteolin,kaempferol,tanshinone IIA,crypt otanshinone and other active components of hawthorn-Salviorrhizapurpura combination have more correlation with disease targets,a nd are the main active components in the treatment of NAFLD.A mong the intersection targets of drug combination and disease,ST AT3,RELA,MAPK1,TP53,AKT1,TNF,ESR1,IL6,RXRA and of her target genes were more associated in PPI network,so the dru g combination acted on the core target of NAFLD.The results of KEGG pathway enrichment showed that hawthorn-Salvia-purpura d rug combination may act on the corresponding targets through can cer pathway,lipid and atherosclerosis pathway,AGE-RAGE pathwa y in diabetic complications and other related pathways.Conclusion:1.The commonly used drugs for treating NAFLD with traditional Chinese medicine include hawthorn,Alisma orientalis,Poria cocos,Salvia miltiorrhiza,Chaihu,Atractylodes macrocephala,Cassia seed,etc;The characteristics of medication are mainly sweet,bitter,and spicy,with a combination of cold and warm;The main treatment method is to strengthen the spleen and soothe the liver,supplemented by the methods of dispelling dampness and phlegm,promoting blood circulation and resolving blood stasis,and clearing heat.2.Hawthorn and cassia seed,as well as hawthorn salvia miltiorrhiza alisma,have a high correlation in the literature prescriptions of traditional Chinese medicine for treating NAFLD,making them commonly used drug combinations.3.Network pharmacological analysis found that quercetin,luteolin,kaempferol,tanshinone ⅡA,cryptotanshinone and other active ingredients in hawkhawn-sal via miltiorrhiza and purpura drug combination.By regulating STAT3,RELA,MAPK1,TP53 and other targets,It is involved in the inhibition of NAFLD-related inflammatory response,oxidative stress,regulation of lipid metabolism,regulation of immune function and other mechanisms,affecting the cancer pathway,lipid and atherosclerosis pathway,AGE-RAGE pathway in diabetes complications and other pathways to improve NAFLD.