| Objective : The incidence of chronic kidney disease in the population is increasing year by year,which has become a serious public health problem endangering human health.Professor Gao Jining has been engaged in the work of kidney disease in traditional Chinese medicine for many years and has rich clinical experience.He is often used to treat chronic kidney disease with rhubarb and leech.In this paper,the complex network relationship of ’drug-compound-target-disease ’ was constructed by network pharmacology research method,and the possible active components and potential targets of rhubarb and leech drugs in the prevention and treatment of chronic kidney disease were predicted,and the mechanism of prevention and treatment of chronic kidney disease was studied.Methods : Firstly,the active compounds of rhubarb and leech were collected by using the TCMSP and literature retrieval.The active compounds were imported into Pub Chem database to obtain their standard compound names and SMILES formats.The effective active compounds meeting the requirements of gatrointestinal absorption and druglikeness characteristics were screened by Swiss ADME platform.The targets of effective active compounds were obtained on Swiss Target Prediction platform and TCMSP database.The above targets were uniformly converted into gene names by Uniprot database,and reorganized.Then,the target proteins related to chronic kidney disease collected from TTD,Drug Bank,Dis Ge NET and OMIM databases were merged to obtain the target proteins related to chronic kidney disease.The jvenn platform was used to obtain the potential key targets of rhubarb and leech in the prevention and treatment of chronic kidney disease.The ’ drug-compound-target-disease ’ network was constructed by Cytoscape3.7.2 software,and the interaction between key target proteins was further clarified by STRING platform.Finally,the selected key targets were imported into DAVID v6.8 database to perform GO analysis and KEGG analysis of key targets.So as to systematically analyze the network pharmacology mechanism of ’ rhubarb-leech ’ drug pair on the prevention and treatment of chronic kidney disease.Results: 1.The effective active compounds and action targets of ‘ rhubarb-leech ’drug pair: A total of 28 effective active compounds meeting the requirements of gatrointestinal absorption and druglikeness characteristics were screened by Swiss ADME platform,27 effective active compounds were screened by rhubarb,and 2 effective active compounds were screened by leech.A total of 675 targets were obtained from Swiss Target Prediction platform and TCMSP database.2.The targets related to chronic kidney disease: 1329 targets related to chronic kidney disease were screened by TTD,Drug Bank,Dis Ge NET and OMIM database.3.The potential key targets of ’ rhubarb-leech ’ drug pair in the prevention and treatment of chronic kidney disease: 67 common targets of ’ rhubarb-leech ’ drug pair in the prevention and treatment of chronic kidney disease were obtained by jvenn platform.3.The ’ drug-compound-target-disease ’ network construction of ’ rhubarb-leech ’drug pair for the prevention and treatment of chronic kidney disease: The ’drug-compound-target-disease ’ network of ’ rhubarb-leech ’ drug pair for the prevention and treatment of chronic kidney disease was constructed based on Cytoscape3.7.2 software.The network contains 98 nodes and 255 edges,including 1 disease node,2 drug nodes,28 active compound nodes and 67 target nodes.The network topology analysis showed that the median values of the betweennesscentrality,closenesscentrality and degree of the compounds were 0.00564757,0.38039216 and 5.5,respectively.A total of 10 active compounds met the screening conditions of core active compounds,namely Eupatin,Piceatannol,Rhapontigenin,Chrysophanol,Emodin,10β-hydroxy-6β-isobutyrylfuranoeremophilane,Physcion,Emodin Anthrone,Rhein and Toralactone.The median values of the betweennesscentrality,closenesscentrality and degree of the targets were 0.00236264,0.00236264 and 2,respectively.The targets on them were PPARG,MMP3,MMP9,CYP2C19,EGFR,ALPL,ABCG2,ABCB1,ADH1 C,MPO,LDHA,MMP2,HDAC8,ADAM17,ACE,RET,FLT1,AHR,EGLN1,TP53,APP,MAPT,ECE1,MME,CYP1A2,SHBG,SLC13A5,and FADS1.The top five eligible values were EGFR,MMP9,MMP2,LDHA and ABCB1.4.The protein-protein interaction networks:The PPI networks was obtained through STRING platform,and it was visualized by Cytoscape3.7.2 software.The median values of the betweennesscentrality,closenesscentrality and degree were 0.00374192,0.7173913 and 40,respectively.The key targets in this network were SIRT1,MMP2,CCL2,PDGFRB,IL1 B,STAT3,TP53,REN,EGFR,FLT1,APP,PPARG,ACE,NOS3,CXCL8,PSEN1,CTNNB1,DPP4,MMP9,TLR4,SPP1,TNF,HIF1 A,ITGB3,VEGFA and MMP3.From the above,EGFR,MMP9,MMP2 are in the core position in the ’drug-compound-target-disease ’ network and PPI networks,which is speculated to be the core targets for the prevention and treatment of chronic kidney disease.5.Enrichment analysis results: 271 biological process items,44 cellular component items and 59 molecular function items were obtained from David database,mainly involving the positive regulation of transcription from RNA polymerase II promoter,plasma membrane and protein binding.Most of the targets were enriched in HIF-1signaling pathway,NOD-like receptor signaling pathway,Toll-like receptor signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,NF-kappa B signaling pathway MAPK signaling pathway and other 56 signaling pathways.Conclusion : In this study,the network pharmacology technology was used to preliminarily explore the complex network process of ’ rhubarb-leech ’ drug pair in chronic kidney disease through multi-component,multi-target and multi-level overall regulation of multiple signaling pathways,playing a synergistic role in anti-inflammatory,anti-fibrosis,anticancer,immune regulation and other mechanisms.It provides an important scientific basis for the prevention and treatment of chronic kidney disease with "rhubarb-leech" drug pair,and has a certain guiding significance. |
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