Based On Network Pharmacology And Metabolomics, The Mechanism Of Liuwei Dihuang Pills In The Treatment Of Diabetic Nephropathy Was Analyzed

Objective:Diabetic nephropathy(DN)is a chronic progressive kidney disease that is mainly characterized by reduced glomerular filtration rate.It is a microvascular complication of diabetes(DM),which can eventually lead to end-stage renal disease and death and threaten human health Despite extensive research on DN,the mechanism remains unclear.The efficacy of the classic drug Liuwei Dihuang Wan in the treatment of DN is recognized,but the mechanism by which it exerts its overall synergy is unclear.Taking this as a clue,this study explored the therapeutic effect of Liuwei Dihuang Wan on DN model and analyzed the possible mechanism of its intervention in DN rats through the network pharmacology and metabolomics of traditional Chinese medicine.The pharmacodynamics and mechanism of Liuwei Dihuang Wan in DN Research provides the basisMethods:SD rats were induced by streptozotocin(STZ)to establish a DN model and intervened with Liuwei Dihuang Wan;fasting blood glucose and renal function biomarkers(urine protein,ACR,serum Cr and BUN content)were measured in each group of rats;Search the chemical constituents of Liuwei Dihuang Wan from the Chinese Medicine Chemical Database(TCMSP),and screen the active ingredients of Liuwei Dihuang Wan through oral bioavailability(OB)and drug-like properties(DL).The database(OMIM)retrieves DN targets,maps Liuwei Dihuang Wan targets to DN targets to obtain potential therapeutic targets,and enriches them through the STRING database,gene ontology(GO)analysis,and the Kyoto Encyclopedia of Genes and Genomes(KEGG).Set analysis and use Cytoscape 3.7.1 to build a component-target-pathway network for Liuwei Dihuang Wan to treat DN;analyze the phenotypic profile of serum metabolism in DN rats by liquid chromatography-mass spectrometry(LC-MS);The Human Metabolome Database(HMDB)finds potential bio marker-related proteins and conducts integrated analysis of network pharmacology and metabolomicsResults:Compared with the DN group,the fasting blood glucose content in the Liuwei Dihuang Wan group was significantly reduced(p<0.01);the levels of urinary protein,ACR,serum Cr and BUN were significantly reduced(p<0.05,p<0.01).A total of 37 active compounds in Liuwei Dihuang Wan were found,among which Kaempferol and Quercetin were the main compounds.21 targets and 63 related pathways were screened out,and the key targets AKT,VEGFA,NOS3,IL6,and SERPINE1 were concentrated in important pathways AGE-RAGE signaling pathway in diabetic complications.Serum metabolomics analysis has obtained 78 different metabolites and 23 metabolic pathways,further screened five linoleic acid metabolism,α-linolenic acid metabolism,glycerophospholipid metabolism,tryptophan metabolism,and arginine and proline metabolism(p<0.05)Metabolic pathway.After integrating the results of metabolomics and network pharmacology,it is concluded that the possible mechanism for Liuwei Dihuang Wan to improve DN rats is to affect serotonin and linoleic acid by targeting HTR3A,CYP3A4,ALOX5,CYP1A1 and GRIA2 proteins And L-glutamic acid synthesis,and then regulate tryptophan metabolism,glycerophospholipid metabolism,arginine and proline metabolism pathways.Conclusion:This study confirms that Liuwei Dihuang Wan can improve fasting blood glucose and renal function of DN model rats and exert pharmacodynamic effects.Based on the analysis methods of network pharmacology and metabolomics,the multi-component,multi-target,and multi-path mechanism of Liuwei Dihuang Wan for DN was clarified.The component-target-metabolism network of Liuwei Dihuang Wan for DN was established.The foundation for the treatment of DN.