Abstract
Background and objectiveColon 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.MethodsThe 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.ResultsSix 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.ConclusionThis 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.
Highlights
With the rapid development of human society and the improvement of life standard, cancer as a growing threat, is the second leading noncommunicable disease of death globally only to cardiovascular disease [1]
285 target genes in total interacting with those putative components were collected, among which 251 were obtained from the Swiss Target Prediction and 34 from TCMSP database
By analyzing Gene Ontology (GO) enrichment, we found that phosphatidylinositol 3-kinase signaling is an important biological process of ginger on regulating cancer-related pathways, which may be contribute to the regulation of PI3K-Akt pathway in this study
Summary
With the rapid development of human society and the improvement of life standard, cancer as a growing threat, is the second leading noncommunicable disease of death globally only to cardiovascular disease [1]. 6-gingerol and 6-shogaol, the representative components derived from ginger, has been reported to preventing cell proliferation against colon cancer, such as Colon-26 tumors [7, 8]. It is unclear whether other ginger components possess the anticancer activity. 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
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