A network pharmacology approach to investigate the pharmacological effect of curcumin and capsaicin targets in cancer angiogenesis by module-based PPI network analysis

Abstract

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.