Exploring the target and molecular mechanism of Astragalus membranaceus in the treatment of vascular cognitive impairment based on network pharmacology and molecular docking

Abstract

Astragalus membranaceus (AM) is a traditional Chinese herbal medicine extensively utilized in vascular cognitive impairment (VCI) treatment. However, due to the complex components of AM, its exact molecular mechanism remains unclear. Therefore, this study investigated the target and molecular mechanism of AM to treat VCI based on network pharmacology and molecular docking. Firstly, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, STITCH, and SwissTargetPrediction were utilized to gather the primary active ingredients of AM. The potential therapeutic targets of VCI were collected through GeneCards, OMIM, and DisGeNET databases. Secondly, the protein-protein interaction network was built using the STRING database. The enrichment analysis of gene ontology and the Kyoto Encyclopedia of Genes and Genome pathways was carried out in the R language. Finally, The network topology calculation of Cytoscape software was combined with module analysis to predict the binding properties of its active ingredients and targets. Twenty effective compounds and 733 targets were screened from AM, among which 158 targets were seen as possible targets of AM to treat VCI. MAPK3 and MMP9 were the critical targets of AM intervention in VCI. The crucial pathways include PI3K/Akt, MAPK, Rap1, and Ras signaling pathways. Besides, calycosin and quercetin might be the potential active compounds of AM for VCI treatment. AM intervenes in VCI through a multi-ingredient, multi-target, and multi-pathway coordination mechanism. These findings provide a foundation for a deeper understanding of the molecular mechanisms by which AM is effective in treating VCI.

Figure 1.

The flow chart for the research.

Figure 2.

Target Wayne diagram of AM and VCI (blue represents VCI and red represents AM). AM = Astragalus membranaceus, VCI = vascular cognitive impairment.

Figure 3.

The PPI network diagram of the 158 key targets of AM treatment of VCI (The darker the color, the greater the connectivity; the larger the circle, the greater the connectivity; the innermost 10 targets are the keys with the highest connectivity target). AM = Astragalus membranaceus, PPI = protein–protein interaction, VCI = vascular cognitive impairment.

Figure 4.

MCODE analysis of potential targets of AM on VCI. (A) Module 1; (B) module 2; (C) module 3; (D) module 4; (E) module 5; and (F) module 6. AM = Astragalus membranaceus, VCI = vascular cognitive impairment.

Figure 5.

GO and KEGG enrichment analysis results (The circle size represents the number of enriched genes. The larger the circle, the more the number of genes. The color represents the adjusted P value. The redder the color, the lower the P value, and the higher the degree of enrichment). GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genome.

Figure 6.

Herbs-active ingredients-targets-signaling pathways-diseases network diagram of AM in the treatment of VCI (Green triangle is the herb. Yellow rectangle is the active ingredient. Blue hexagon is the two key targets. Red ellipse is the 12 critical pathways of VCI, and gray diamond is the name of the disease). AM = Astragalus membranaceus, VCI = vascular cognitive impairment.

Figure 7.

MAPK3 and calycosin molecular docking diagram after adjustment.

Figure 8.

MMP9 and quercetin molecular docking diagram after adjustment.