Simulation analysis and pharmacokinetic evaluation of atractylide I for the treatment of diabetic nephropathy

摘要

Objective:The study aims to investigate the molecular mechanism and druggability of Atractylide I(AT-I)for the treatment of diabetic nephropathy(DN)using network pharmacology,molecular docking,and pharmacokinetic analysis.Method:Multiple databases and service platforms were used to predict and screen the potential genes of AT-I for the prevention and treatment of DN.Further,gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses were performed on the genes to evaluate the mechanism of AT-I against DN.The protein interaction network was constructed by the STRING database,and the key gene targets of AT-I against DN were screened by Cytoscape software.The binding activity of AT-I with the essential target proteins was analyzed by molecular docking technique.Finally,the pharmacokinetic parameters of AT-I were evaluated to determine its druggability.Result:AT-I has 45 drug action targets intersecting with DN targets,which may be the potential targets of AT-I for the prevention and treatment of DN.The enrichment analysis indicated that gene expression regulation,insulin resistance,hypoxia inducible factor-1 signaling pathway,tumor necrosis factor signaling pathway,and PI3K-Akt signaling pathway determine the biological mechanism of AT-I in the prevention and treatment of DN.Further,network pharmacology and molecular docking results indicated that key genes such as AKT1,MAPK8,EGFR,MAPK1,MMP9,and MTOR bind well with AT-I,while AKT1 is probably the primary target gene of AT-I against DN.Pharmacokinetic analysis showed that AT-I conforms to Lipinski’s rule of five drug-like properties,has good gastrointestinal absorption,can pass the blood-brain barrier,and has superior biological properties.Conclusion:AT-I has desirable druggability and multi-target,multi-pathway,and multi-mechanism activity against DN.This study provides an important basis for future research on the activity of AT-I against DN.