A network pharmacology-based investigation on the bioactive ingredients and molecular mechanisms of Gelsemium elegans Benth against colorectal cancer

BMC Complementary Medicine and Therapies

Bingqing Zhang¹  Ling Yang²  Zhichang Zhao³  Wancai Que³  Maobai Liu³  Maohua Chen³  Yu Cheng³  Hongqiang Qiu⁴ 

[1]College of Pharmacy, Fujian Medical University, 350004, Fuzhou, People’s Republic of China

[2]Department of Pharmacy, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China

[3]Department of Pharmacy, Fujian Medical University Union Hospital, 29 Xin Quan Rd, Gulou, 350001, Fuzhou, Fujian, People’s Republic of China

[4]Department of Pharmacy, Fujian Medical University Union Hospital, 29 Xin Quan Rd, Gulou, 350001, Fuzhou, Fujian, People’s Republic of China

[5]College of Pharmacy, Fujian Medical University, 350004, Fuzhou, People’s Republic of China

关键词: Gelsemium elegans Benth;    Colorectal cancer;    Network pharmacology;    Mechanism;   

DOI  :  10.1186/s12906-021-03273-7

来源: Springer

【 摘 要 】

BackgroundColorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. Gelsemium elegans Benth (GEB) is a traditional Chinese medicine commonly used for treatment for gastrointestinal cancer, including CRC. However, the underlying active ingredients and mechanism remain unknown. This study aims to explore the active components and the functional mechanisms of GEB in treating CRC by network pharmacology-based approaches.MethodsCandidate compounds of GEB were collected from the Traditional Chinese Medicine@Taiwan, Traditional Chinese Medicines Integrated Database, Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine, and published literature. Potentially active targets of compounds in GEB were retrieved from SwissTargetPrediction databases. Keywords “colorectal cancer”, “rectal cancer” and “colon cancer” were used as keywords to search for related targets of CRC from the GeneCards database, then the overlapped targets of compounds and CRC were further intersected with CRC related genes from the TCGA database. The Cytoscape was applied to construct a graph of visualized compound-target and pathway networks. Protein-protein interaction networks were constructed by using STRING database. The DAVID tool was applied to carry out Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis of final targets. Molecular docking was employed to validate the interaction between compounds and targets. AutoDockTools was used to construct docking grid box for each target. Docking and molecular dynamics simulation were performed by Autodock Vina and Gromacs software, respectively.ResultsFifty-three bioactive compounds were successfully identified, corresponding to 136 targets that were screened out for the treatment of CRC. Functional enrichment analysis suggested that GEB exerted its pharmacological effects against CRC via modulating multiple pathways, such as pathways in cancer, cell cycle, and colorectal cancer. Molecular docking analysis showed that the representative compounds had good affinity with the key targets. Molecular dynamics simulation indicated that the best hit molecules formed a stable protein-ligand complex.ConclusionThis network pharmacology study revealed the multiple ingredients, targets, and pathways synergistically involved in the anti-CRC effect of GEB, which will enhance our understanding of the potential molecular mechanism of GEB in treatment for CRC and lay a foundation for further experimental research.

【 授权许可】

CC BY