A network pharmacology approach to investigate the pharmacological effect of curcumin and capsaicin targets in cancer angiogenesis by module-based PPI network analysis
- 3 Downloads
Curcumin and capsaicin play a vital role in anti-inflammatory and anti-cancer mechanism as they are used as therapeutic drugs/adjuvants. Our previous study including many reports explored strong inhibitory effect of curcumin and capsaicin on lipopolysaccharide-induced polymorph blood mononuclear cells (PBMCs) and cancer cells. Therefore, a systematic study was carried out to identify the potential protein targets of curcumin and capsaicin in cancer as well as angiogenesis through network pharmacology and molecular docking approaches. In the present investigation, we employed integrative prediction of cancer targets of curcumin and capsaicin through the ChEMBL and STITCH databases, followed by network construction, network topology, gene ontology, pathway enrichment and molecular docking studies. The gene ontology analysis made it possible to identify a library of possible cancer targets of curcumin (34 targets) and capsaicin (35 targets). Based on topological analysis, the unique target of curcumin and capsaicin was proposed by identifying essential bottleneck/hub node MAPK1. Further, PANTHER gene set analysis was used to distinguish the biologically enriched pathways in top identified gene clusters (MAPK1). To validate the identified target, high-throughput molecular docking was employed as both molecules curcumin and capsaicin along with standard ulixertinib were docked against MAPK1 to understand the binding interaction. The docking results of MAPK1 with curcumin (− 7.6 kcal/mol) has shown good inhibitory effect similar to that of standard control ulixertinib (− 8.1 kcal/mol) compared with capsaicin (− 6.0 kcal/mol). Based on the molecular interaction, MAPK1 identified through the network pharmacology approach could be a probable target of curcumin and capsaicin to prevent angiogenesis in cancer.
KeywordsNetwork pharmacology Drug–target interaction Curcumin Capsaicin Molecular docking
The authors are thankful to the Registrar, Kuvempu University, Shankaraghatta-577 451 for providing facilities to complete this work.
Compliance with ethical standards
Conflict of interest
The authors have declared that there is no conflict of interest.
- Rose PW, Prlić A, Bi C, Bluhm WF, Christie CH, Dutta S, Green RK, Goodsell DS, Westbrook JD, Woo J, Young J, Zardecki C, Berman HM, Bourne PE, Burley SK (2015) The RCSB Protein Data Bank: views of structural biology for basic and applied research and education. Nucleic Acids Res 43:D345–D356CrossRefGoogle Scholar
- Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C (2015) STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43:D447–D452CrossRefGoogle Scholar
- Trott O, Olson AJ (2010) AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455–461Google Scholar