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. 2022 Jul 15:2022:3389180.
doi: 10.1155/2022/3389180. eCollection 2022.

Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer's Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology

Qingsong Liu  1 , Shaofeng Wang  2 , Yanwei Hao  3 , Jiaxin Li  3 , Wei Li  2 , Yi Zhang  1 , Bin Li  3
Affiliations

Active Compounds and Targets of Yuanzhi Powder in Treating Alzheimer's Disease and Its Relationship with Immune Infiltration Based on HPLC Fingerprint and Network Pharmacology

Qingsong Liu et al. Evid Based Complement Alternat Med. .

Abstract

Background: Yuanzhi powder (YZP) has been extensively investigated as a natural prescription with therapeutic benefits for Alzheimer's disease (AD). However, its active compounds and underlying immune mechanism for treating AD are still unclear. This study aimed to investigate the immune mechanism of YZP against AD through high-performance liquid chromatography (HPLC)-based network pharmacology and gene chip technology.

Methods: Active components of YZP were obtained from HPLC and public databases. Subsequently, GSE5281, GSE28146, GSE29378, and GSE97760 from the Gene Expression Omnibus (GEO) database were downloaded to extract AD difference genes (DEGs). The active components-targets network and protein interaction network were then constructed by Cytoscape. The biological processes and signaling pathways, which implicate the targets of YZP for AD, were analyzed using the ClueGo Cytoscape plug-in. Molecular docking experiments were performed to verify the affinity of targets and ligands. Ultimately, the link between the hub genes and immune cell infiltration was assessed via CIBERSORT.

Results: 83 YZP active compounds and 641 DEGs associated with AD, including quercetin, berberine, 3,6'-disinapoylsucrose, coptisine, and palmatine, were evaluated. We showed that FOS, CCL2, and GJA1 were the core targets and that the gap junction is an essential signaling pathway in YZP for AD. Furthermore, the AD group had a higher infiltration level of naïve B cells and resting CD4 memory T cells, as determined by the CIBERSORT. Notably, the immune cells-targets network demonstrates that GJA1 and GRM1 are intimately related to naïve B cells and plasma cells.

Conclusions: YZP may help treat AD by targeting proteins with key active compounds to regulate naïve B cells and plasma cells. Our results demonstrate a new immune mechanism for treating AD with YZP.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Fingerprint of Yuanzhi Powder (YZP) and AD differential genes (DEGs) screening. (a) Fingerprinting of YZP. Peak 5- 3,6′-disinapoylsucrose, peak 14- coptisine, peak 15- palmatine, peak 16- berberine. (b) PCA analysis before batch effect removal. (c) PCA analysis following batch effect removal. (d) Volcano map for DEGs. Red nodes represent upregulated genes, blue nodes represent downregulated genes, and black nodes represent no DEGs. (e) Heatmap of DEGs from AD and normal tissue. Red indicates higher gene expression, and blue indicates lower gene expression.
Figure 2
Figure 2
Screening and enrichment analysis of overlapping genes. (a) Venny map showing YZP-AD gene mapping. (b) PPI network exhibiting. (c) The enrichment of GO BP analyses of DEGs based on ClueGO enrichment analyses. (d) Enrichment of KEGG pathway via ClueGO enrichment analyses. ClueGO revealed correlations among channels by calculating the kappa coefficients.
Figure 3
Figure 3
Active Components-Targets Network. The circle represents the composition of the herbal medicine, the rectangle represents the target point, and the redder color of the rectangle node indicates the number of degrees.
Figure 4
Figure 4
Molecular docking of crucial targets and ligands. (a) Heat map showing the results of molecular docking. (b) The conformations for FOS and coptisine. (c) The conformations for CCL2 and 3,6′-disinapoylsucrose. (d) The conformations for GRIA1 and coptisine. (e) The conformations for GRM1 and coptisine.
Figure 5
Figure 5
The immune infiltration between AD and controls and immune regulatory network. (a) The box plots show the relative percentage of different types of immune cells between AD patients and non-AD patients. (b) The difference in immune infiltration between AD (red) and controls (blue) (P values <0.05 indicated statistical significance). (c) The heat map shows the correlation in the infiltration of innate immune cells by CIBERSORT. (d) YZP-AD interaction plot of genes and immune-related molecules.
Figure 6
Figure 6
The flowchart of the study. The active compounds of YZP were conducted with HPLC fingerprint and various bibliographical databases and HPLC. Next, the genes associated with Alzheimer's disease were filtered by the GSE5281, GSE28146, GSE29378, and GSE97760. The active components-targets network and protein interaction network were then constructed by Cytoscape. The biological processes and signaling pathways were analyzed using the ClueGo Cytoscape plug-in. Molecular docking experiments were performed to verify the affinity of targets and ligands. Ultimately, the link between the hub genes and immune cell infiltration was assessed via CIBERSORT.
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