Medication Regularity And Mechanisms Of Traditional Chinese Medicine In Im Proving Insulin Resistance Of Non-alcoholic Fatty Liver Disease:A Study Based On Data Mining And Network Pharmacology

Objective:For summarizing the rules of drug compatibility,and finding out the core traditional Chinese medicine for improving NAFLD with IR,Data mining technology was used to analyze the prescriptions of traditional Chinese medicine which improve IR in NAFLD patients.Network pharmacological analysis of core Chinese medicine was conducted to study the mechanism of improving NAFLD with IR,so as to provide reference and guidance for clinical medication and theoretical research.Methods:CNKI,VIP,Wanfang,PubMed and Cochrane database were searched to collect the prescriptions of traditional Chinese medicine for improving IR in NAFLD patients.Excel 2019 and TCM Inheritance Support System 3.0 were used for statistical analysis of the frequency,four qi and five taste,efficacy of the collected prescriptions.In order to find the core traditional Chinese medicine and prescriptions for improving IR in NAFLD patients,IBM SPSS Statistics 18.0 was used to conduct association rule and cluster analysis of data.TCMSP,ETCM and Chemistry Database were searched for collecting the main chemical constituents and action targets of core traditional Chinese medicine.Therapeutic targets of NAFLD with IR were obtained by searching GeneCards,OMIM and Drugbank databases.The intersection of drug targets and disease targets,namely key targets,was obtained by using Excel 2019,and key targets were imported into Cytoscape 3.8.2 to draw the network diagram of medicine,active ingredients-disease targets.Key targets were imported into STRING and Cytoscape 3.8.2 to build PPI network and conduct topological analysis,to obtain the core targets of core medicine to improve IR in NAFLD patients.Key targets were imported into Metascape,an online analysis tool,for enrichment analysis of GO function and KEGG pathway.Results:A total of 83 literatures were included,involving 83 prescriptions,including 153 kinds of herbs,with a total of 853 times of medication frequency.Among them,the most frequently used drugs were tonifying deficiency,followed by clearing damp and promoting diuresis,clearing heat,activating blood circulation and removing blood stasis,and so on.The statistical results of drug frequency showed that Hawthorn fruit,Oriental waterplantain rhizome,Danshen root,Indian bread,Cassia seed,Largehead atractylodes rhizome,Chinese thorowax root,Dried tangerine peel,Turmeric root tuber and Lotus leaf were the most commonly used drugs.The results of association rule analysis showed that Hawthorn fruit-Largehead atractylodes rhizome and Cassia seed,Hawthorn fruit-Cassia seed and Danshen root were the core medicational combinations.Cluster analysis showed that Sijunzi decoction and Erchen decoction were the most commonly used decoction.A total of 82 active ingredients were screened,including 7 ingredients of Hawthorn fruit,13 ingredients of Cassia seed,60 ingredients of Danshen root and 4 ingredients of Largehead atractylodes rhizome.181 targets of Hawthorn fruit,60 targets of Cassia seed,137 targets of Danshen root and 18 targets of Largehead atractylodes rhizome were obtained.After screening,1503 targets of NAFLD and IR were obtained.A total of 124 key targets were obtained by intersecting the target of core herbs with the target of disease.Topological analysis results showed that AKT1,IL6,TNF,TP53,IL1B,VEGFA,CASP3,ESR1 and STAT3 were the core targets.GO functional enrichment analysis showed that potential targets were mainly concentrated in oxidative responses in biological processes,membrane pits in cellular components,and binding of transcriptional coactivators of molecular functions.KEGG enrichment analysis showed that Cassia seed,Hawthorn fruit,Largehead atractylodes rhizome and Danshen root could improve NAFLD and IR through cancer,metabolic,immune and oxidative stress pathways.Conclusion:"Deficiency syndrome" is the most common syndrome in NAFLD with IR patients,followed by "dampness","heat" and "blood stasis",suggesting that it may be the main pathological features of NAFLD with IR.The core herbs and prescription also reflected that the core treatment of NAFLD with IR were invigorating spleen and qi,promoting blood circulation,removing dampness and turbidizing.In addition,the core medicine had theadvantages of multiple components,multiple targets and multiple pathways in the treatment of NAFLD patients with IR,and it is predicted that Hawthorn fruit,Largehead atractylodes rhizome,Cassia seed,Danshen root may regulate metabolic,immune,and oxidative stress pathways to treat IR in patients with NAFLD,providing a theoretical basis for further research on its mechanism.