Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

Abstract

Background and objective: Colon cancer is occurring at an increasing rate and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent for colon cancer. This study was aimed to identify the bioactive components and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach.

Methods: The putative ingredients of ginger and its related targets were discerned from the TCMSP and Swiss target prediction database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape 3.8.1. Finally, Discovery studio software was employed to confirm the key genes and active components from ginger.

Results: Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified through PPI network analysis. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, and JAK2 were viewed as the most important genes, which were validated by molecular docking simulation.

Conclusion: This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-targets and multi-pathways with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.

Keywords: 1-Monolinolein; Colon cancer; GO enrichment; Ginger; KEGG enrichment; Molecular docking.

Fig. 1

The detailed flowchart of the study design

Fig. 2

The representative pictures of Venn diagram and protein-protein network. a 118 intersection genes; b a complete protein-protein network; c one protein-protein cluster with 37 nodes and 179 edges; d one protein-protein cluster with 17 nodes and 42 edges

Fig. 3

Enrichment analysis on BPs of 34 key targets. a The bubble chart; b the visualization analysis of BPs

Fig. 4

The bubble chart of KEGG enrichment based on 34 key targets

Fig. 5

The drug-components-targets-pathways-disease network

Fig. 6

The heat map of the docking score

Fig. 7

The represented results for the action mode of active compounds with 5 targets protein using molecular docking. a Action mode of 6-gingerol (MOL002467) with target TP53 (PDB ID: 5O1F); b Action mode of sitosterol (MOL000359) with target HSP90AA1 (PDB ID: 4BQG); c-e Action mode of 1-monolinolein (MOL002464) with target MAPK8 (PDB ID: 4E73), JAK2 (PDB ID: 3KCK), and CASP3 (PDB ID: 1RE1), respectively; f Action mode of beta-sitosterol (MOL000358) with target ERBB2