Exploring The Medication Rules And Mechanisms For The Treatment Of Diabetes Combined With Dyslipidemia Based On Data Mining And Network Pharmacolog

Purpose:Based on modern literature,this paper explores the rule of drug use of traditional Chinese medicine in the treatment of diabetes with dyslipidemia in recent 20 years,and discusses the target,signal pathway and mechanism of core drugs in the treatment of "astragalus-salvia miltiorrhiza-hawthorn",so as to provide a reference for the treatment of diabetes with dyslipidemia and experimental research.Material and method:1.Search the literature on the treatment of diabetes with dyslipidemia by oral administration of traditional Chinese medicine in the past 20 years(August 2002 to August 2022)in the three databases of Zhiwang,Wanfang and Weipu.Use Note Express document management software to conduct preliminary screening of the documents,and then read through the Enab criteria to screen out the final research documents.The composition,nature,taste and meridian tropism of the drugs were counted by Excel tables,and the database of TCM prescriptions was established.SPSS statistical software was used to carry out frequency analysis,cluster analysis and association rule analysis,summarize the medication rules of traditional Chinese medicine prescriptions in treating diabetes with dyslipidemia,and screen out the core drug group.2.The Chinese herbal medicine system pharmacology platform(TCMSP)and the Chinese medicine encyclopedia database(ETCM)are used to screen the main active ingredients of the core drug group,and the Swiss Target Prediction database is used to find the possible target of the active ingredients of the core drug,and the disease target is obtained from the gene databases such as Genecards,Disgenet,OMIM,and the name of the target obtained is unified and standardized by using the Uniprot database,The We Chat website is used to intersect the active ingredient target with the disease target and draw the Wayne diagram.The core drug-active component-target network diagram is constructed and analyzed through the Cytascape v3.9.1 software.The core drug-treatment target information is put into the STRING 11.5 database to obtain the protein interaction(PPI)network diagram,and then the network is topologically analyzed and further drawn through the Cytascape v3.9.1 software,The GO function and KEGG pathway enrichment analysis of intersection targets were carried out using the biological information database DAVID,the analysis results were visualized using the We Chat website,and the correlation network diagram of KEGG pathway and the target of "treating different diseases together" was drawn using the Cytoscape v3.9.1 software.Finally,the mechanism of the core drug group in treating diabetes with dyslipidemia was obtained.Results:1.Data mining results:In this study,136 effective documents were finally included in the compliance standard,142 prescriptions were extracted,involving 151 traditional Chinese medicines,and the cumulative use frequency reached 1485 times.Among them,there are 28 traditional Chinese medicines with a frequency ≥ 20 times.The top 10 traditional Chinese medicines ranked in frequency were astragalus(82 times),salvia miltiorrhiza(79 times),hawthorn(72 times),alisma orientalis(52 times),poria cocos(50 times),pueraria lobata(44 times),atractylodes macrocephala(42 times),raw rehmannia(40 times),yam(37 times),and coptis chinensis(35times).The statistical results of the efficacy of traditional Chinese medicine showed that the top 5 drugs ranked in the frequency were tonic drugs,antipyretic drugs,blood-activating and stasis-removing drugs,diuretic and damp-removing drugs,and antipyretic drugs.After the efficacy was subdivided,the top 10 drugs ranked in the frequency were tonic drugs,blood-activating and menstruating drugs,diuretic and detumescence drugs,heat-clearing and blood-cooling drugs,antipyretic drugs,yin tonifying drugs,wind-heat dispersing drugs,blood tonic drugs,heat-clearing and fire-purging drugs,and damp-removing drugs.Among the four gas frequencies,cold drugs(556 times)ranked first,followed by warm and mild drugs.Among the five flavors,sweet drugs(907 times)ranked first,followed by bitter and bitter drugs.The liver channel(780 times)and spleen channel(770 times)ranked first,followed by lung and stomach channels.According to cluster analysis,28 high-frequency traditional Chinese medicines can be divided into five groups: pinellia ternate-tangerine peel-liquorice-bupleurum chinense-alisma orientalis-atractylodes macrocephala-hawthorn-poria cocos,astragalus membranaceus-salvia miltiorrhiza-pueraria lobata-chinese yam-rhizoma polygoni,safflower-peach kernel-red peony-ligusticum chuanxiong-angelica,atractylodes macrocephala-radix scrophulariae-coptis chinensis-raw rehmannia root-ophiopogon japonicus-trichosanthes-codonopsis pilosula,cassia seed-polygonum multiflorum.The association rule analysis of traditional Chinese medicine obtained 16 groups of drug combinations,of which the support and confidence of the two groups of salvia miltiorrhiza-radix astragali and hawthorn-radix astragali-radix salviae miltiorrhizae were high.It was proposed that radix astragali,radix salviae miltiorrhizae and hawthorn were the core drug groups of this study.2.Network pharmacology results:A total of 101 main active components of the core drug group were screened,and 773 drug targets were predicted.After the intersection of drug target and 70 common targets of two diseases,21 "treatment of different diseases" targets are obtained.These 21 targets correspond to 64 active components,among which the more important active components include(24s)-24-propylcholesterol-5-en-3 β-Alcohol α-Aromaticol,Zidanshensu C,Dehydroporic acid β-Sitosterol,stigmasterol,arachidonic acid,etc.The protein interaction(PPI)network analysis obtained four core target proteins,namely TNF,PPARA,PPARG and CYP3A4.There are 18 pathways related to the treatment of this disease in the core drug group,including PPAR signaling pathway,bile secretion,lipid and atherosclerosis,insulin resistance,and steroid hormone biosynthesis.Conclusion:1.In clinical treatment of diabetes with dyslipidemia,drugs for invigorating qi and activating blood circulation,clearing heat and removing dampness are mainly used,drugs for sweet and warm taste and bitter and cold taste are mostly used,and meridian tropism is mainly based on the liver and spleen meridians;Association rule analysis showed that the core drug group was:astragalus-salvia miltiorrhiza-hawthorn.2.The mechanism of core drug group "astragalus miltiorrhiza hawthorn" in treating diabetes with dyslipidemia is to use the(24s)-24-propylcholester-5-en-3 contained in it β-Alcohol α-Vanillin,rhodanin C,dehydrodontoporic acid β-Glutosterol and other active ingredients affect TNF,PPARA,PPARG,CYP3A4 and other targets through regulating PPAR signaling pathway,bile secretion,lipid and arterial Congee,insulin resistance,steroid hormone biosynthesis and other signaling pathways in biological processes such as cholesterol metabolism,monoterpene metabolism,heterocyclic metabolism,response to lipid,long-chain fatty acid transport,etc.