Based On Data Mining And Network Pharmacology, Traditional Chinese Medicine Compound Prescriptions For DPN Drug Use And Mechanism Analysis

Purpose:Based on the modern literature,this paper explores the medication rules of DPN,and explores the target,signal pathway and mechanism of core drugs in the treatment of DPN,so as to provide reference for the screening of traditional Chinese medicine and further experimental research of DPN.Method: The relevant literatures were searched in CNKI,CBM,Wanfang and other databases with reasonable retrieval mode,and the retrieval period was set from January 2010 to August 2020.The case report,case analysis and medical case summary of DPN treated by traditional Chinese medicine compound prescription were screened out to establish literature research database,and then data analysis was carried out to excavate the prescription rules and core drug pairs.The effective components and pharmacological information of the core drug pairs were obtained from tcmsp database,and the corresponding targets were obtained.After the target database was established,the target matching and network construction were carried out.The core targets were screened by using Cytoscape 3.7.1 software.Finally,gene go and KEGG pathway enrichment analysis was performed to speculate the mechanism of the core drug on the treatment of DPN.Results:1 Mata mining results According to the inclusion and exclusion criteria,370 valid articles were obtained.A total of 187 traditional Chinese medicines were extracted from 370 prescriptions for DPN,and 37 of them were used more than 20 times,including Astragalus,angelica,Ligusticum chuanxiong,earthworm,Caulis Spatholobi,etc.The total frequency of four Qi is 4861 times,the most frequent is warm medicine 1877 times,followed by cold and flat;the total frequency of five flavors is 5974 times,the most is sweet taste 2082 times,followed by bitter taste and pungent taste;the total frequency of channel tropism is 9489 times,statistics show that the frequency of liver channel,heart channel and spleen channel is 2525 times,1640 times and 1629 times respectively.When the support and confidence were set to "90%" and "0.9",52 drug combinations with frequency > 90 were obtained,including 12 traditional Chinese medicines.The drug network was simplified,and the core drug pair was "Astragalus Angelica".According to the number of prescriptions,set the correlation degree and punishment degree as 8 and 2 respectively to get the correlation degree between the two drugs,and adjust the value of result to 4.Through the drug combination with high correlation degree,the system automatically analyzes and obtains 10 groups of potential core drug groups.Each combination matches each other,and five new prescription combinations are obtained: tangerine peel,dannanxing,Pinellia ternata,Jineijin;Astragalus membranaceus,Caulis Spatholobi,rhubarb,earthworm;Uncaria rhynchophylla,Haifengteng,luoshiteng,Lonicera japonica;jujube,Danshen,asarum,earthworm;medlar,Achyranthes bidentata,sangsheng,Clematis.2 Network pharmacology research Results In TCMSP database,the effective components of core drug pair "Astragalus Angelica" were searched,and 20,2 effective components and 209,29 targets were obtained by OB ?30%,DL ? 0.18 criteria.Through genecards database,4777 potential targets of DPN were obtained by searching with "diabetic peripheral neuropathy" as the subject word,and 71 targets were obtained after intersection with active component targets.Twelve active components of Astragalus Angelica were screened by using Cytoscape 3.7.1 software.The target degree values of quercetin,kaempferol and isorhaetin were 59,25 and 15 respectively.These active components may play an important role in the treatment of DPN by Astragalus angelica.Application of string database and R Project software,according to the count value,the top 20 key targets of Astragalus Angelica in the treatment of DPN were screened and listed for visual analysis.Combined with the target compounds derived from Cytoscape 3.7.1,the core targets were EGFR,ESR1,rela,NF-? B,MAPK,PPARG,etc.,which indicated that the above targets played an important role in the network of Astragalus Angelica in the treatment of DPN.Gene go results showed that there were 1058 items with BP P < 0.05,involving response to steroid hormone,response to xenobiotic stimulus,response to ketone, etc.There were 17 items with cell composition(CC)P < 0.05,including membrane raft,transcription factor complex,etc.There were 76 items with molecular function(MF)P < 0.05,mainly including nuclear receptor activity,etc.KEGG enrichment results showed that it mainly included PI3K-Akt,MAPK,AGE-RAGE,TNF,HIF1 and other signaling pathways.Conclusion:1.The clinical medication of traditional Chinese medicine compound in the treatment of DPN is mainly Yiqi Huoxue Tongluo,which is in line with the basic pathogenesis of DPN.Most of the drugs belong to liver,spleen and heart,and most of them are sweet and warm drugs and bitter and cold drugs.They have the functions of Supplementing Qi and nourishing Yin,activating blood circulation and dredging collaterals,reflecting the method of treating both the symptoms and the root causes.By using association rules mining method and simplifying drug network,the core drug pair is Astragalus angelica.There are five new levels of DPN,but they are still valuable for clinical application.2.Based on the network pharmacology method,the potential mechanism of core drug pair in the treatment of DPN is obtained: the main components of core drug are quercetin,kaempferol,isorhamnetin,etc.,which act on GFR,ESR1,rela,NF-? B,MAPK,PPARG and other targets in PPI network,and regulate PI3K-Akt,MAPK,AGE-RAGE,TNF,HIF1 and other signaling pathways in the cell metabolism,inflammatory response,immune stress of DPN patients and so on.