Mechanism Of Astragalus Membranaceus For Diabetic Kidney Disease By WGCNA And Network Pharmacology

Background: Diabetic kidney disease(DKD)is a common microvascular complication of diabetes and the main cause of end-stage renal disease.As a complex disease,the pathogenesis of DKD involves multiple genes and complex signaling pathways.At present,the effect of single-target intervention drugs is very limited.Astragalus(AM)is widely used in DKD in many Chinese herbal compound preparations.Research purpose: Network pharmacology based on data analysis can conduct integrated research on the relationship between candidate molecules,signaling pathways,drugs,target genes and diseases involved in the occurrence and development of DKD;provide new molecular markers for the diagnosis of DKD substance,explaining the mechanism of AM in the treatment of DKD.Research methods: Using early-late DKD genome-wide expression profiling data,weighted gene co-expression network analysis(WCGNA),to obtain phenotype-related key modules,network construction,enrichment analysis,and identification of hub nodes,key to identify key through network pharmacology Drug components and targets,systematically elucidate the molecular network mechanism of early-late DKD progression and drug targets of AM in the treatment of DKD.Results: In early DKD,up-regulated genes were enriched: mitochondrial translation,biological processes related to the oxidative respiratory chain and ATP biosynthesis,mitochondria and subcellular structures in mitochondria,NADH dehydrogenase(Co Q)activity,ribosome and cytochrome-c oxidase active structural components,oxidative phosphorylation,metabolic pathways,Alzheimer’s disease,Parkinson’s disease,Huntington’s disease and myocardial contractility;down-regulated gene enrichment: transcriptional and cellular responses to external stimuli Responserelated,nuclear and transcription factor complexes,transcription factor activity and binding,TNF signaling,MAPK signaling,cytokine-cytokine receptor interactions,and Toll-like receptor signaling.In advanced DKD,the up-regulated genes were enriched in: mainly including signal transduction,immune response,inflammatory response and extracellular matrix organization,membrane,extracellular region,TNF-activated receptor activity,receptor activity and receptor binding,cellular Factor-cytokine receptor interaction,chemokine signaling pathway,NF-kappa B signaling pathway,cell adhesion molecule,B cell receptor and T cell receptor pathway;down-regulated gene enrichment: metabolic process,redox process and Transmembrane transport,exosomes,cytoplasmic membrane,membrane and mitochondria,etc.,oxidase activity,calcium ion binding and protein homogenization activities and metabolic pathways.MMP2,MMP9,IL1 B,IL6,CXCL8,PPARA,JUN,and VEGFA play important roles in key pathways of DKD pathogenesis and progression,and are involved in processes such as anti-fibrosis,anti-inflammatory,immune response inhibition,and anti-oxidative stress.5 key active ingredients were screened from AM,quercetin,kaempferol,7-O-methylisomicrovestol,formononetin and isorhamnetin,key targets such as MMP9,MMP2,DPP4,JUN,CXCL8,IL6,PTGS2,FOS,IL1 B,PPARA,TP53,and VEGFA,etc.;enrichment analysis showed that these targets are closely related to inflammation,angiogenesis,oxidative stress,rheumatoid arthritis,etc.process.Conclusion: The key gene modules closely related to the clinical features of DKD were analyzed using WGCNA.Network pharmacology to obtain key targets of AM active components such as MMP9,MMP2,DPP4,JUN,CXCL8,IL6,PTGS2,FOS,IL1 B,PPARA,TP53 and VEGFA,etc.;targeting inflammation,angiogenesis,oxidative stress,Processes such as rheumatoid arthritis may be the molecular mechanism of AM in the treatment of DKD.