Exploring the mechanism of ShenGui capsule in treating heart failure based on network pharmacology and molecular docking: A review

Abstract

ShenGui capsule (SGC), as a herbal compound, has significant effects on the treatment of heart failure (HF), but its mechanism of action is unclear. In this study, we aimed to explore the potential pharmacological targets and mechanisms of SGC in the treatment of HF using network pharmacology and molecular docking approaches. Potential active ingredients of SGC were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform database and screened by pharmacokinetic parameters. Target genes of HF were identified by comparing the toxicogenomics database, GeneCards, and DisGeNET databases. Protein interaction networks and gene-disorder-target networks were constructed using Cytoscape for visual analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes were also performed to identify protein functional annotations and potential target signaling pathways through the DAVID database. CB-DOCK was used for molecular docking to explore the role of IL-1β with SGC compounds. Sixteen active ingredients in SGC were screened from the traditional Chinese medicine systems pharmacology database and analysis platform, of which 36 target genes intersected with HF target genes. Protein-protein interactions suggested that each target gene was closely related, and interleukin-1β (IL-1β) was identified as Hub gene. The network pharmacology analysis suggested that these active ingredients were well correlated with HF. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that target genes were highly enriched in pathways such as inflammation. Molecular docking results showed that IL-1β binds tightly to SGC active components. This experiment provides an important research basis for the mechanism of action of SGC in the treatment of HF. In this study, the active compounds of SGC were found to bind IL-1β for the treatment of heart failure.

Figure 1.

The flowchart of this study. CTD = comparing the toxicogenomics database, GO = gene ontology, HF = heart failure, KEGG = Kyoto Encyclopedia of Genes and Genomes, PPI = protein-protein interaction, SGC = ShenGui capsule, TCMSP = the traditional Chinese medicine systems pharmacology database and analysis platform.

Figure 2.

Target genes for heart failure. CTD= = comparing the toxicogenomics database.

Figure 3.

Common target genes of HF and SGC. HF = heart failure, SGC = ShenGui capsule.

Figure 4.

PPI network (the nodes indicate 36 genes, and the black connecting lines represent the interactions of genes). PPI = protein-protein interaction.

Figure 5.

Top 5 genes (the top 5 genes obtained according to the MCC algorithm in the PPI network). PPI = protein-protein interaction, TNF = tumor necrosis factor.

Figure 6.

Disease-drug-compound-target genes network (red hexagon represents the disease HF, purple square represents the drug SGC, blue dot represents the active compounds, pink V represents the components of SGC; yellow diamond is the name of target genes). HF = heart failure, SGC = ShenGui capsule.

Figure 7.

Top 20 results of GO and KEGG pathway enrichment analysis of target genes. (A) Enriched BP of target genes. (B) Enriched CC of target genes. (C) Enriched MF of target genes. (D) Enriched KEGG pathways of target genes. CC = cellular component, GO = gene ontology, KEGG = Kyoto Encyclopedia of Genes and Genomes, MF = molecular function.

Figure 8.

Molecular docking of the receptors and their ligands. (A) ent-Epicatechin to IL-1β. (B) β-sitosterol/sitosterol to IL-1β. (C) FA to IL-1β. (D) (+)-Catechin to IL-1β. (E) Mandenol to IL-1β. (F) (−)-Taxifolin to IL-1β. (G) Taxifolin to IL-1β. (H) DNOP to IL-1β. (I) Myricanone to IL-1β. (J) Perlolyrine to IL-1β. (K) Ginsenoside rh2 to IL-1β. (L) Wallichilide to IL-1β.