| Objective:Utilizing data mining of clinical literature on external treatment of Venous leg ulcers（VLU）with traditional Chinese medicine,the core drugs were extracted,and the medication rules and characteristics of external treatment of VLU with traditional Chinese medicine were analyzed and summarized.Network pharmacology research was carried out on the excavated core drugs to predict key genes and main participation pathways,hoping to provide targeted reference for the experiment of VLU principle of external treatment of traditional Chinese medicine.Methods:Study 1:Collect the clinical literature of the clinical literature of external treatment of VLU with traditional Chinese medicine from January2000 to December 2022 by searching searching Pubmed,CNKI,Wan Fang Data and VIP database.Data mining was carried out with the help of traditional Chinese medicine inheritance auxiliary platform（V3.0）,including four natures,five flavors,meridian tropism and efficacy of drugs;drug frequency,association rules,cluster analysis,according to data results and literature analysis of modern physicians of traditional Chinese medicine external treatment of VLU clinical experience,medication rules,and refine the core drug combination.Study 2:To explore the mechanism of external treatment of VLU with traditional Chinese medicine based on network pharmacology.Seeking out the effective components of core drugs by TCMSP database and literature,predicting related targets by using Pub Chem and Swiss Target Prediction databases.Disease targets were collected in Gene Cards,Therapeutic Target Datebase,Dis Ge NET,An Online Catalog of Human Genes and Genetic Disorders and Drug Bank databases.The core drug targets and disease targets were intersected and compared by using the bioinformatics platform to obtain relevant targets.Cytoscape（V3.9.0）software was used to draw the’core drug-effective component-disease-target’TCM regulation network diagram.The intersection targets were used to establish a protein interaction network using the String platform and topological analysis was performed using the Cyto NCA plug-in of Cytoscape software to obtain the core PPI network.Metascape database was used for GO analysis and KEGG enrichment analysis of related intersection targets.According to the P-value value,the important pathways of active components involved in the treatment of VLU were screened and discussed.Results:1.There are 110 literatures that meet the criteria screened by the inclusion and exclusion criteria.A total of 97 prescriptions were included,and154 drugs were counted.The total frequency of use was 703 times.According to the frequency of drugs,the top 5 were Phellodendron chinense,Angelica sinensis,Lithospermum erythrorhizon,Borneolum Syntheticum and Angelica dahurica.The results of cluster analysis of prescriptions were divided into three groups.The first group was:borneol,cinnabar,calamine,gypsum,borax,a total of 24;the second group:Phellodendron,Scutellaria,Coptis,Rhubarb,Borneol,a total of 22;the third group:Phellodendron,Angelica,Lithospermum,Angelica,Frankincense,a total of 51.The support degree was set to 15（15.46%）,and the confidence degree was 0.6 for drug association rule analysis to obtain 5 high-frequency drug pair combinations of drug use patterns.The highest frequency was frankincense and myrrh.The confidence level was unchanged,and the support degree was set to 10（10.30%）.A total of 28 data were obtained,including 15 traditional Chinese medicines.The network graph association rule drugs included Phellodendri Chinensis Cortex,Angelicae Sinensis Radix,Angelicae Dahuricae Radix,Arnebiae Radix,Taraxaci Herba,Draconis Sanguis,Glycyrrhizae Radix et Rhizoma,Rhubarb,etc.2.The results of core drug treatment VLU network pharmacology showed that 65 active components of core drugs and 359 effective chemical components targets of core drugs were obtained.650 disease-related targets were obtained;after intersection and comparison,78 potential targets were obtained;through the construction of protein interaction network diagram and topology analysis,the potential core targets（PTGS2,PIK3 CA,MAPK1,RELA,EGFR,MTOR,MMP1）and the effective chemical components of core drugs（osmanthuside H,arnebinone,alkannin beta,beta-dimethylacrylate,phellopterin,quercetin）were obtained.After GO enrichment analysis and KEGG enrichment analysis,432 related biological processes and 160 related signaling pathways were obtained.Conclusion（s）:1.Through clinical literature data mining,the core drug composition of traditional Chinese medicine external treatment of VLU is Cortex Phellodendri,Radix Angelicae Sinensis,Radix Arnebiae,Radix Angelicae Dahuricae,Frankincense.According to the analysis of the results,modern doctors use traditional Chinese medicine for external use to treat VLU according to its syndrome characteristics,with the methods of removing blood stasis and promoting granulation,clearing heat and removing rot,and promoting blood circulation and tonifying deficiency.3.According to the results of the network pharmacology research,it is clarified that the key compounds contained in the core drugs,such as shikonin（arnebinone,and Alkannin beta,beta-dimethylacrylate）,osmanthuside H,phellopterin and quercetin,may change the expression of PIK3 CA,PTGS2,MAPK1,DRD2 and other key targets by regulating NOD-like receptor signaling pathway,Ca2+and other signaling pathways,so as to intervene in cell apoptosis,regulate inflammatory response,promote angiogenesis,optimize collagen deposition,and further play a therapeutic role in VLU. |
