Unveiling the Potential of Garcinia Atroviridis Root-Derived Phenolic Compounds Against Breast Cancer: Isolation, Network Pharmacology and In-Silico Approaches

This study aimed to isolate and characterize bioactive compounds from the roots of Garcinia atroviridis and evaluate their potential anticancer activity, particularly against breast cancer (BC), through network pharmacology and in-silico approaches. Compounds were isolated from the ethyl acetate (EtOAc) extract of G. atroviridis roots using chromatographic and spectroscopic techniques. Their anticancer potential was assessed through network pharmacology analyses, including target prediction, protein–protein interaction (PPI) network construction, and enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Molecular docking and 150-nanosecond molecular dynamics (MD) simulations were conducted to evaluate the binding affinity and stability of compound-target interactions. Five phenolic compounds, namely atrovirisidone, 1,3,5-trihydroxy-2-methoxyxanthone, GB1a, volkensiflavone, and morelloflavone, were successfully identified. Network analyses highlighted HIF1A, ITGB1, RET, HDAC2, and MAPK1 as key molecular targets. GO and KEGG analyses revealed that these targets are associated with cancer-related pathways. All compounds demonstrated strong binding affinities to HIF1A, with docking energies ranging from − 33.02 to − 51.19 kcal/mol, outperforming standard ligands. Among them, morelloflavone exhibited the strongest interaction and stable binding, as confirmed by MD simulations. The phenolic compounds from G. atroviridis, particularly morelloflavone, exhibit significant potential as anticancer agents by modulating HIF1A-related pathways. These findings support further investigation of morelloflavone as a lead compound for breast cancer therapeutics.