Integrated analysis and network pharmacology approaches to explore key genes of Xingnaojing for treatment of Alzheimer's disease.

BACKGROUND

Alzheimer's disease (AD), as a neurodegenerative condition, is one of the leading causes of dementia. Our study aims to explore the key genes of Xingnaojing (XNJ) for treatment of AD by integrated microarray analysis and network pharmacology.

METHODS

The differentially expressed genes (DEGs) were identified in AD compared with normal control. According to these DEGs, we performed the functional annotation, protein-protein interaction (PPI) network construction. The network pharmacology was used to explore the potential targets of XNJ in the treatment of AD. The expression level of selected candidate genes was validated by quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS

A total of 1,424 DEGs (620 genes were upregulated and 804 genes were downregulated) between AD and normal control were obtained. The functional annotation results displayed that neuroactive ligand-receptor interaction, regulation of actin cytoskeleton, Estrogen signaling pathway and notch signaling pathway were significantly enriched pathways in AD. Comparing the target genes of four active ingredients, a total of 16 shared genes were found. Among which, HTR2A and ADRA2A were also enriched in pathway of neuroactive ligand-receptor interaction. The expression of 4 DEGs (SORCS3, HTR2A, NEFL, and TAC1) was validated by qRT-PCR. Except for TAC1, the other 3 DEGs in AD were consistent with our integrated analysis.

CONCLUSIONS

The results of this study may provide novel insights into the molecular mechanisms of AD and indicate potential therapeutic targets for AD.