Methods: The active components and targets of Huang Qi Si Jun Zi Tang were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database.
The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of Huang Qi Si Jun Zi Tang were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of Huang Qi Si Jun Zi Tang were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE.
Results: Compound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc.
There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of Huang Qi Si Jun Zi Tang, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells.
Conclusion: Huang Qi Si Jun Zi Tang was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in Huang Qi Si Jun Zi Tang may regulate multiple signalling pathways through AChE, which might play a therapeutic role in Alzheimer’s disease.