Antiproliferative Effects of <i>Ajuga orientalis</i> Methanolic Extract: In Vitro and In Silico Insights

Abstract Ajuga orientalis , a perennial herb from the Lamiaceae family, is traditionally used in Jordanian folk medicine for its therapeutic properties. This study evaluates the phytochemical profile, cytotoxicity, drug‐likeness, and molecular docking of the methanolic extract of A. orientalis to explore its potential as a source of novel therapeutic agents. GC‐MS analysis identified 21 compounds, including oleic acid methyl ester (27.1%) and palmitic acid (12.5%). The extract demonstrated significant concentration‐dependent cytotoxicity against RAW264.7 macrophage cells, with an IC 50 of 91.5 µg/mL. Molecular docking studies revealed fundamental interactions of phytochemicals with cancer‐related proteins, including VEGFR2 and TLR4/MD‐2, showing strong binding affinities. Notably, 1,7‐di(2,5‐dimethylphenyl)‐2,2,4,4,6,6‐hexamethyl‐1,3,5,7‐tetraoxa‐2,4,6‐trisilaheptane and the 2TBDMS derivative of 4‐hydroxybenzeneacetic acid exhibited promising interactions, indicating potential for inhibiting angiogenesis and modulating immune responses. Drug‐likeness evaluation of 18 compounds showed that 11 meet the criteria for oral bioavailability, though some challenges for drug development remain. This research underscores the therapeutic potential of A. orientalis compounds in cancer treatment and immune modulation, suggesting further experimental validation and development of these bioactive compounds.