Mechanism Of Zhenwu Decoction In Treating Diabetic Nephropathy Based On Network Pharmacology And Molecular Docking

Diabetic nephropathy(DN)is a typical complication of acute microvascular nephropathy in patients with diabetes mellitus(DM).Its clinical manifestations are hyperglycemia,hypertension,proteinuria and severe systemic edema.The traditional Chinese medicine compound Zhenwu Decoction(ZWD)is widely used in the treatment of DN in China,and has a long history,but the specific pharmacological effect is still unclear.The purpose of this study is to reveal the pharmacological effect and mechanism of ZWD in the treatment of DN by using network pharmacology and molecular docking methods.Materials and methods: in this study,TCMSP,TCMID and BATMAN-TCM databases,according to ADME principle,the effective components of five traditional Chinese medicines in ZWD were screened out,and the functional targets of active components were extracted with drug bank and Uni Prot database.The target genes related to DN were collected by Gene Cards and OMIM databases,and then the active component targets and disease targets were mapped by Venn.Then,the "Drug-Target-Disease" network and ZWD target protein interaction network(PPI)were established by using STRING database and Cytoscape software.To further explore the mechanism and therapeutic effect of ZWD on DN,Go and KEGG signaling pathways are analyzed for the key targets in the PPI network.Finally,using molecular docking technology,the key activity compounds in ZWD are connected with the core target proteins for the treatment of DN.From the perspective of molecular mechanism,molecular docking model is established to predict the effective components and targets of ZWD,and to predict the binding mode and affinity.Results: a total of 70 potential activity compounds and 106 potential targets were screened and analyzed from ZWD drugs,and 57 intersection genes were obtained by Venn mapping.The results of association network analysis showed that kaempferol,beta-sitosterol,stigmasterol,hederagenin,(+)-catechins and paeoniflorin were the main active compounds in ZWD,which can directly act on eight potential key core targets of IL6,AKT1,PTGS2,JUN,CASP3,CAT,MAPK8 and AHR,which are involved in the regulation of heme binding,tetrapyrrole binding,response to lipopolysaccharide,Oxidoreductase activity,organelle or cell membrane composition and other biological processes.They mainly regulate MAPK signalingpathway,NF-k B signaling pathway and HIF-1 signaling pathway,thus playing a role in immune regulation,oxidative stress and stress response and other biological processes.The results of molecular docking indicated that the main active components of ZWD were able to bind with various target proteins for DN treatment(S > 4.5),indicating that ZWD has the characteristics of multi-component and multi-target;the molecular docking results also suggest that Paeoniflorin and Stigmasterol may be the key effective component of ZWD in treating DN.Conclusion: This study reveals that ZWD can play a multi drug active component,multi-functional target and multi-channel intervention to regulate DN characteristics through immune regulation,oxidative stress and stress response,which is the theoretical basis for clinical development and utilization of ZWD in the treatment of DN.