To Explore The Mechanism Of Leech Regulate Podocytopathy Based On Network Pharmacology Method

Objective: To elucidate the key mechanism of Chinese medicine leech on podocyte related diseases from cellular and molecular levels through network pharmacology and molecular docking technology,and to provide theoretical reference for the subsequent clinical application and basic research of leech intervention in podocyte disease.Methods: TCMID and Sym Map database were searched,then Swiss ADME database was used to screen the active ingredients of Hirudo leeches,and relevant literature was collected to supplement the active ingredients.Pharmmapper database was used to predict the potential targets of each active ingredient.Gene Cadrs and Dis Ge NET databases were searched to obtain the targets of podocyte lesions and related diseases.The drug and disease target names were officially calibrated through Uniprot database,and then the intersection of the two was obtained using Venny 2.1 online mapping tool.Subsequently,STRING database and Cytoscape 3.7.1 software were used to make PPI(protein-protein interaction)network diagram and construct the "TCM-active compound-target-disease" network diagram,from which key targets and key components were screened for subsequent molecular docking simulation experiments.GO functional annotation and KEGG pathway analysis of intersecting target lines were performed using DAVID database to predict the mechanism of leech intervention in podocyte related diseases.Finally,molecular docking software was used to perform molecular docking between the key active components and the target to simulate and verify the analysis results.Results: A total of 44 active compounds,164 active ingredient action targets,1154 podocyte related disease targets and 60 drug and disease intersection targets were obtained.The active compounds included Hirudin,Crocin,Ursolic Acid,etc.,and the targets with high degree value were ALB,EGFR,SRC,ESR1,CASP3,etc.GO analysis yielded 219 Biological processes,mainly involving proteolysis,negative regulation of apoptosis,and positive regulation of cell proliferation,and 42 Cellular components.There are 57 Molecular functions,including enzyme binding,receptor binding,transmembrane receptor protein tyrosine kinase activity,protein binding,steroid binding,etc.,which are mainly concentrated in extracellular regions,cytoplasm,adhesive plaques,membrane rafts,etc.The results of KEGG analysis suggested that the enrichment degree of cancer-related pathways,IL-17 signaling pathway,MAPK signaling pathway,lipid and atherosclerosis,fluid shear stress and atherosclerosis signaling pathways was high.Subsequent molecular docking experiments indicated that the three key active ingredients(Hirudin,Crocin,Ursolic acid)obtained by analysis had good binding activity with five key targets(ALB,EGFR,SRC,ESR1,CASP3).Conclusion: The results of this study indicate that many active components of Chinese medicine hirudin(e.g.Hirudin,saffron,ursolic acid)can regulate various signaling pathways(e.g.,cancer-related pathways,IL-17 signaling pathways,MAPK signaling pathways,lipids and atherosclerosis,fluid shear stress,atherosclerosis,etc.)and participate in various biological processes(e.g.,proteolysis and apoptosis processes)Negative regulation,positive regulation of cell proliferation,etc.)to influence multiple targets(such as ALB,EGFR,SRC,ESR1,CASP3)to exert their role in the intervention of podocytopathy-related diseases.This complete mechanism of action is based on the characteristics of TCM’s multi-pathway and multi-target intervention in diseases,which provides a theoretical basis for the research and development of new drugs and a new direction for the treatment of diseases.