Comparative Network Pharmacology Analysis of Ethyl Acetate, n-Butanol and Residual Fractions of Stachytarpheta jamaicensis Against Lung Cancer

Stachytarpheta jamaicensis (L.) Vahl is a pantropical medicinal plant with documented antioxidant, anti-arthritic, and antimicrobial properties, but its anticancer potential has been evaluated only against breast and cervical cancer cell lines, and no network pharmacology framework has been applied to it. This study comparatively evaluated its ethyl acetate, n-butanol, and residue leaf-extract fractions against lung cancer. Eleven phytochemicals were prioritized across the three fractions based on drug-likeness and reported bioactivity. Predicted targets overlapped lung-cancer-associated genes to a similar extent in every fraction (83.06%, 82.54%, and 82.23% for ethyl acetate, n-butanol, and residue respectively). Protein-protein interaction analysis identified HIF1A as the only hub gene common to all three fractions, with AKT1, SRC, EGFR, and BCL2 each recurring in two; these five were prioritized for docking. Pathway enrichment converged on kinase-mediated cancer pathways, with Pathways in Cancer, apoptosis, and EGFR tyrosine kinase inhibitor resistance enriched in all three fractions. Molecular docking, with every receptor grid validated by redocking of its co-crystallized ligand, identified Silychristin (n-butanol) as the leading compound, returning scores comparable to the matched reference inhibitors at two validated kinase targets: −9.43 kcal/mol at SRC (dasatinib − 9.51) and − 9.30 kcal/mol at EGFR (erlotinib − 9.25). Secoisolariciresinol (residue) followed at − 8.91 kcal/mol at SRC. At HIF1A and BCL2 the reference inhibitors did not separate from the compound set, and these targets were not used to compare fractions. Anticancer-relevant target engagement is therefore distributed across all three fractions rather than concentrated in one.