A Network Pharmacology-Based Identification Study on the Mechanism of Xiao-Xu-Ming Decoction for Cerebral Ischemic Stroke

Abstract

Objective: We used the network pharmacological analysis method to explore the mechanism of multicomponent, multitarget, and multiway actions of Xiao-Xu-Ming decoction (XXMD) for cerebral ischemic stroke (CIS), which provided a basis on the research of innovative drugs.

Method: We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) to retrieve the active ingredients and targets of 12 herbs of XXMD; we used the Gene Expression Omnibus (GEO) database of the National Center for Biotechnology Information (NCBI) to screen for differentially expressed genes in CIS to obtain the disease targets of CIS and to intersect it with the action targets of XXMD, and then the target drug efficacy is obtained. We used Cytoscape 3.6 software to construct the drug-active ingredient-action target interaction network of XXMD to treat CIS and conduct protein-protein interaction (PPI) network and topology analysis. The action target Gene Ontology (GO) biological processes and metabolic pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) of XXMD to treat CIS were enrichment analyzed with R software.

Result: We screened out 226 active ingredients and 3646 action targets for XXMD. Among them, XXMD to treat CIS has 144 active ingredients, 12 targets, and proteins in the core network of PPI having STAT3, HIF1A, etc. Pathway enrichment analysis was based on the GO and KEGG biological processes involved in active oxygen metabolism, smooth muscle cell proliferation, cytokine production, angiogenesis, redox coenzyme metabolism, and oxidative stress. The main action processes are significantly associated with CIS signal pathways involved in microRNAs, ovarian steroid hormones, NF-кB signaling pathway, Th17 cell differentiation pathway, HIF-1 signaling pathway, folic acid synthesis pathway, galactose metabolism, and fructose and mannose metabolism.

Conclusion: This study initially clarified the main targets and pathways of XXMD in the treatment of CIS, which can lay the foundation for further research on its pharmacological effects.

Figure 1

Heatmap of differentially expressed genes in whole-blood samples of patients with CIS and healthy people. Note: C, whole-blood samples of healthy people; B, whole-blood samples from patients with CIS; red, high gene expression; green, low gene expression.

Figure 2

Volcano plot of differentially expressed genes in whole-blood samples of patients with CIS and healthy people. Note: black dots, no differential genes; red dots, upregulation of genes in patients with CIS; green dots, upregulation of genes in healthy people.

Figure 3

Drug-active ingredient-target interaction network of XXMD in the treatment of CIS.

Figure 4

PPI construction and topological analysis of XXMD in the treatment of CIS.

Figure 5

The distribution of GO enrichment items in the biological processes (BP) of the targets of XXMD in the treatment of CIS.

Figure 6

The distribution of GO enrichment items in the molecular function (MF) of the targets of XXMD in the treatment of CIS.

Figure 7

KEGG pathway analysis bubble chart of the targets of XXMD in the treatment of CIS.

Figure 8

Relationship between KEGG pathways and targets of XXMD in the treatment of CIS.