Pharmacological Analyses of the Mechanisms of Morinda officinalis How. in the Treatment of Alzheimer's Disease

Objective: To analyze the potential targets and mechanism of action underlying the therapeutic action of Morinda officinalis How. against Alzheimer's disease (AD) based on network pharmacology, molecular docking, and gene expression omnibus (GEO) data. Methods: Using the traditional chinese medicine systematic pharmacology database and analysis platform (TCMSP), the main active components of Morinda officinalis were identified, and the targets of Morinda officinalis were obtained via SwissTargetPrediction. AD-related targets were obtained from DrugBank, PathCard, Chemogenomic Database, and PubChem databases. Then, Venn diagram was used to obtain the common targets of both Morinda officinalis and AD. Cytoscape 3.8.0 was used to construct ''component-target'' network diagrams of the targets. The protein-protein interaction (PPI) network diagrams, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways of the targets were analyzed. The molecular docking of key components and targets was performed using AutoDock, and the docking results were visualized using Pymol and Discovery Studio. Finally, the expressions of key AD-related target genes were analyzed using the GEO database from Alzdata. Results: Fifty main active components of Morinda officinalis were predicted. A total of 636 action targets and 674 AD-related targets were obtained, including 124 common targets related to AD treatment. GO enrichment analysis yielded protein phosphorylation, positive regulation of phosphorylation, cellular response to nitrogen compounds, regulation of hydrolase activity and cellular response to chemical stress. KEGG enrichment analysis showed that Alzheimer's disease as the most significant pathway. Molecular docking revealed that the five core components of Morinda officinalis, including 2-hydroxy-1,5-dimethoxy-6-(methoxymethyl)-9,10-anthraquinone, 1-hydroxy-3-methoxy-9,10-anthraquinone, rhododendron-A, rubiadin and rubiadin-1-methyl ether, exhibited strong binding with the three core targets, EGFR, PARP1 and FTO. The expression of Egfr was significantly (P<0.05) upregulated in AD patients, while Parp1 and Fto were significantly (P<0.05) downregulated. Conclusion: Morinda officinalis might be useful in regulating AD progression via multiple components, targets and pathways.