Objective  To explore the active components, targets, and mechanisms of Fuzhisan in the treatment of Alzheimer's disease (AD).

Methods  The effective components of Fuzhisan were determined through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the related target proteins were obtained. The key targets affecting AD were predicted using the GeneCards database. The intersection targets of Fuzhisan and AD were obtained using the Venny 2.1.0 platform. The drug-component-target network was constructed using Cytoscape 3.9.1 software. The intersection targets were imported into the STRING database to construct a protein-protein interaction network and screen the key targets. The common targets of the drug and disease were analyzed for enrichment using the Metascape database. Molecular docking was performed with AutoDock 4.2.6 software for the main effective components of Fuzhisan and the key targets of AD, and the results were visualized using PyMOL 2.4.0 software.

Results  A total of 58 active components of Fuzhisan were obtained. A number of 3 652 AD related targets were obtained with a screening criterion of Score ≥ 6.8, and there were 105 intersection targets between the disease and the drug. Gene Ontology (GO) enrichment analysis showed that there were 1 468, 61 and 2 339 entries for biological process, cellular component, and molecular function, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis yielded 184 pathways. Molecular docking results indicated that the effective components of Fuzhisan, such as kaempferol, wogonin, baicalein, β-sitosterol, and stigmasterol, had good binding activity with the key targets TP53, TNF, AKT1, IL^-1β, and IL-6.

Conclusion  Fuzhisan can exert therapeutic effects on AD through multiple components, multiple targets and multiple pathways.

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