OBJECTIVE To investigate the mechanism of Yishen Huazhuo decoction(YHD) in treating Alzheimer’s disease(AD) through network pharmacology and molecular docking techniques, followed by experimental validation.

METHODS The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature searchs were used to identify the components and targets of the compound prescription, while the GeneCards database was employed to retrieve the disease-associated targets. A Venn diagram was drawn to extract the intersecting targets shared between the prescription components and diseases. The STRING database was utilized to construct protein-protein interaction(PPI) network. Cytoscape 3.7.2 was applied to establish the “traditional Chinese medicine-disease-intersecting targets” network. The DAVID database was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis. Molecular docking was conducted using the AutoDock Tools molecular simulation software. In this study, APP/PS1 transgenic mice were used as research objects, and the histopathological changes of hippocampus were detected by HE staining. Western blotting and PCR were used to detect the expression of key factors of PI3K/AKT/GSK-3β signaling pathway in the hippocampus of mice.

RESULTS The core targets obtained through network pharmacology screening included AKT1, TNF, IL6 and other core targets, and the signaling pathways mainly included PI3K/AKT and so on. Molecular docking results showed that kaempferol, quercetin and β-sitosterol had high affinity to the targets. The results of animal experiments showed that YHD could alleviate the histopathological changes in the hippocampus of mice, up-regulated expression of PI3K/AKT/GSK-3β signaling pathway.

CONCLUSION The YHD can improve nerve damage in AD mice, and its mechanism is related to the activation of the PI3K/AKT/GSK-3β signaling pathway, thereby offering theoretical foundation for its clinical application.