Explore the mechanism of Astragalus membranaceus and Poria cocos drug pair in improving immunity based on network pharmacology

Abstract

The aim of this study was to investigate the key targets and molecular mechanisms of the drug pair Astragalus membranaceus and Poria cocos (HFDP) in the treatment of immunity. We utilized network pharmacology, molecular docking, and immune infiltration techniques in conjunction with data from the GEO database. Previous clinical studies have shown that HFDP has a positive impact on immune function. We first identified the active ingredients and targets of HFDP from the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database, respectively. Next, we retrieved the differentially expressed genes (DEGs) related to immunity from the GEO databases. The intersection targets of the drugs and diseases were then analyzed using the STRING database for protein-protein interaction (PPI) network analysis, and the core targets were determined through topological analysis. Finally, the intersection genes were further analyzed using the DAVID database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, by analyzing the expression and prognostic survival of 12 core targets, 5 core target genes were identified, and molecular docking between the hub genes and immunity was performed. Finally, we used the CIBERSORT algorithm to analyze the immune infiltration of immunity genes In this study, 34 effective ingredients of HFDP, 530 target genes, and 568 differential genes were identified. GO and KEGG analysis showed that the intersection genes of HFDP targets and immunity-related genes were mainly related to complement and coagulation cascades, cytokine receptors, and retinol metabolism pathways. The molecular docking results showed that the 5 core genes had obvious affinity for the active ingredients of HFDP, which could be used as potential targets to improve the immunity of HFDP. Our findings suggest that HFDP is characterized by "multiple components, multiple targets, and multiple pathways" in regulating immunity. It may play an essential role in regulating immunity by regulating the expression and polymorphism of the central target genes ESR1, JUN, CYP3A4, CYP2C9, and SERPINE1.

Figure 1.

Flowchart of the current research study.

Figure 2.

DEGs and drug target acquisition. (A) Bar graph of potential protein targets of active phytochemicals in HFDP and regulated genes of DEGs. (B) The volcano of DEGs. (C) Venn diagram of the intersection of the HFDP target and immunity genes. (D)The heat map of intersection genes. (E) Intersection of up-regulated and down-regulated genes of DEGs by HFDP drug targets respectively. (F) Bar graph of 19 down-regulated and up-regulated genes. DEGs = differentially expressed genes, HFDP = Astragalus membranaceus and Poria cocos drug pair.

Figure 3.

Screening core components and core objectives of HFDP in the treatment of immunity. (A) Intersection PPI network interaction map constructed based on STRING website. (B) The PPI network of the 43 intersecting targets was constructed using Cytoscope software. (C) Screening the top 12 core genes in the network according to the degree. (D) The degree of top 12 core genes was drawn by bar graph. (E) Interaction network diagram of component-intersection targets constructed based on Cytoscape 3.9.1 software. (F) The histogram shows the degree value of the top 27 core components. HFDP = Astragalus membranaceus and Poria cocos drug pair, PPI = protein-protein interaction.

Figure 4.

GO and KEGG enrichment analysis. (A) GO enriched analysis of HFDP treatment of immunity, including BP, MF, and CC. (B)KEGG enriched analysis of HFDP treatment of immunity. (C)PPI network diagram of KEGG pathway and core gene. (D)GSEA plot based on GSE174570. (E)Molecular mechanism diagram of core target therapy for immunity. BP = biological process, CC = cellular component, MF = molecular function, GO = gene ontology, GSEA = gene set enrichment analysis, HFDP = Astragalus membranaceus and Poria cocos drug pair, KEGG = Kyoto Encyclopedia of Genes and Genomes, PPI = protein-protein interaction.

Figure 5.

Immune infiltration. (A)Box diagram of clinical relevance analysis of core targets based on GEPAI database. (B)Violin plot of clinical relevance analysis of core targets based on GEPAI database. (C)Copy number diagram of clinical relevance analysis of core targets based on GEPAI database. (D) Prognostic analysis map of clinical correlation analysis of core targets based on GEPAI database. (E) Immunoinfiltration analysis diagram.

Figure 6.

Molecular docking. (A–F) The molecules and drugs with the lowest docking energies are visualized. (G) The docking energy of 5 core targets and 8 core components in 3-line table. (H) Molecular docking energy heat map of 5 core targets and 8 core components.

Figure 7.

Mechanism of HFDP in the treatment of immunity. HFDP = Astragalus membranaceus and Poria cocos drug pair.