Exploring the material basis and mechanism of action of tempeh against Alzheimer's disease based on bioconfidence analysis and kinetic simulation
Objective To investigate the material basis and mechanism of action of tempeh against Alzheimer's disease(AD)using raw letter analysis and kinetic simulation methods.Methods The GEO database was used to screen the original AD dataset,and GEO2R and Venny online tools were used to analyze the differential genes and draw volcano and Wayne diagrams.Metascape database was used to complete GO analysis and KEGG signaling pathway analysis of the intersecting differential genes,and protein-protein interaction(PPI)analysis of the intersecting differential genes was performed using String database.The chemical constituents of tempeh were collected through the ingredient database,and the molecular docking and molecular dynamics simulations of the constituents and key genes that met the conditions for drug-like screening were performed using Discovery Studio,and the intermolecular interaction patterns and action energy curves of the optimal docking combinations were analyzed.Results Three AD datasets were obtained through GEO database screening,and 22 common differentially expressed genes(DEGs)were obtained.The Metascape database showed that the DEGs were not only involved in biological processes such as neuronal cell bodies and neuronal projection endpoints,but also related to multiple mechanistic pathways such as neuroactive ligand and receptor pathways.The String database analysis yielded the top-ranked SYT1 and GFAP as key gene targets.After database collection and ADMET screening,11 compounds in tempeh met the screening criteria,including apigenin from tempeh.By analyzing the 2D planar maps,it was found that the molecule-to-protein interaction was mainly through hydrogen bonding,π-alkyl binding to the active interaction pocket of the target proteins,and combined with the results of molecular dynamics simulations,the van der Waals force ΔEvdw played a major role,and electrostatic interactions played a complementary role.Conclusion Apigenin and 11 other components in tempeh interact with targets in the neuroactive ligand-receptor pathway and GABAergic synaptic signaling pathway through hydrogen bonding,hydrophobic interactions,van der Waals forces,and electrostatic interactions,thus exerting their therapeutic effects in the treatment of AD.
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