Mechanisms of Morindae Officinalis Radix in Treatment of Cognitive Dysfunction Based on Network Pharmacology and Molecular Docking
Objective To analyze the potential targets and mechanism of action underlying the therapeutic action of Morindae Officinalis Radix(MOR)against cognitive dysfunction(CD).Methods The active ingredients,action targets and Crohn's disease(CD)targets of MOR were retrieved using the databases TCMSP,OMIM,Disgenet and GeneCards.The common targets of the active ingredient targets and CD targets of MOR were taken,and the STRING database and Cytoscape 3.9.1 software were used to construct the network diagram of active ingredients of MOR-common targets for treating CD and the protein-protein interaction network diagram(PPI),and to screen the key compounds and key targets.The enrichment analysis of Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways was carried out through the Database for Annotation,Visualization and Integrated Discovery(DA-VID),and the Cytoscape 3.9.1 software was used to draw the network diagram of ingredients-targets-pathways to predict the action mechanism of the key targets.The structures of the ac-tive ingredients and target proteins were respectively obtained from the databases Pubchem and PDB,and imported into the Autodock 4.2 software for docking verification.Results A total of 20 MOR active ingredients,283 action targets,1904 CD-related genes,103 common targets of both MOR and CD,and 21 key targets related to CD treatment were obtained.AKT1,BCL2,EG-FR,CASP3,GSK3B,ESR1,HIF1A ranked the top 7.GO analysis showed that the mechanism of action of MOR for the treatment of CD involves the cellular response of β-amyloid protein,pep-tidyl tyrosine phosphorylation,learning and memory,protein phosphorylation,etc.KEGG pathway is mainly enriched in three disease-related pathways:cancer,endocrine,and neurodegenera-tive.The binding energies of the targets AKT1,BCL2,CASP3,GSK3B,and HIF1A to the compo-nents rhodopsin-A and/or 1-hydroxy-3-methoxy-9,10-anthraquinone were≤-5.0 Kcal/mol.Conclusion The treatment of CD with MOR may exert its effect by regulating multiple targets of the AKT1/GSK3B/BCL2/CASP3 pathway through the oxidation/phosphorylation/apoptosis cas-cade reaction of rhodopsin-A,1-hydroxy-3-methoxy-9,and10-anthraquinone.
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