Mechanistic exploration of bioactive constituents in Gnetum gnemon for GPCR-related cancer treatment through network pharmacology and molecular docking

Abstract

"G Protein-Coupled Receptors (GPCRs) are integral membrane proteins that have gained considerable attention as drug targets, particularly in cancer treatment. In this study, we explored the capacity of bioactive compounds derived from Gnetum gnemon (GG) for the development of of pharmaceuticals targeting GPCRs within the context of cancer therapy. Integrated approach combined network pharmacology and molecular docking to identify and validate the underlying pharmacological mechanisms. We retrieved targets for GG-derived compounds and GPCRs-related cancer from databases. Subsequently, we established a protein-protein interaction (PPI) network by mapping the shared targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to predict the mechanism of action of these targets. Molecular docking was conducted to validate our findings. We identified a total of 265 targets associated with GG-derived bioactive compounds for the treatment of GPCRs-related cancer. Functional enrichment analysis revealed the promising therapeutic effects of these targets on GPCRs-related cancer pathways. The PPI network analysis identified hub targets, including MAPK3, SRC, EGFR, STAT3, ESR1, MTOR, CCND1, and PPARG, which demonstrate as treatment targets for GPCRs-related cancer using GG-derived compounds. Additionally, molecular docking experiments demonstrated the strong binding affinity of gnetin A, gnetin C, (-)-viniferin, and resveratrol dimer, thus inhibiting MAPK3, SRC, EGFR, and MTOR. Survival analysis established the clinical prognostic relevance of identified hub genes in cancer. This study presents a novel approach for comprehending the therapeutic mechanisms of GG-derived active compounds and thereby paving the way for their prospective clinical applications in the field of cancer treatment."