A network pharmacology-based study on key pharmacological pathways and targets of Qi Fu Yin acting on Alzheimer's disease

Abstract

Background: Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by progressive cognitive dysfunction and memory loss. Qi Fu Yin is mainly used to treat dementia, particularly AD, in the clinic, but its comprehensive mechanisms are not known.

Objective: In this research, we aimed to investigate the mechanisms of Qi Fu Yin in AD by network pharmacology and molecular docking.

Methods: First, the chemical constituents in Qi Fu Yin were obtained from five databases and classified according to their structure. Targets of chemical constituents and AD-related targets were also collected from the databases. Then, overlapping genes between Qi Fu Yin and AD were identified by intersection analysis. MetaCore was used to gather enrichment information. Combination synergy analysis was performed by Cytoscape. After ligand-receptor docking, the binding affinity was verified by ADP-Glo™ kinase assay and fluorescence resonance energy transfer (FRET) assay.

Results: We found 12 classes with 977 components in Qi Fu Yin. A total of 511 compounds and 577 potential target proteins in Qi Fu Yin were found to be related to AD. The pathways of Qi Fu Yin in AD included oxidative stress and immune response. There was the best binding affinity between 11 pairs of genes and compounds. Furthermore, CDK5 was inhibited by nepetin with an IC₅₀ of 3.172 μM and kaempferol with an IC₅₀ of 2.659 μM. Ceanothic acid and 18 beta-glycyrrhetinic acid inhibited GSK3β, and the IC₅₀ values were 8.732 μM and 8.06 μM, respectively.

Conclusion: Qi Fu Yin might alleviate Tau hyperphosphorylation by nepetin, kaempferol, ceanothic acid and 18 beta-glycyrrhetinic acid.

Keywords: Alzheimer's disease; CDK5; GSK3β; Molecular docking; Network pharmacology; Qi Fu Yin.