In Vitro and In Silico Evaluation of <i>Sideritis Pisidica</i> : Insights into Biological Potential in Melanoma Cancer Cells

Abstract This study explored the phytochemical profile and anti‐inflammatory and anticancer properties of S. pisidica extract. The phytochemical constituents of the extract were analyzed. Cytotoxicity of the plant extract was determined by MTT assay on G361 cells. The cytotoxic effects on human melanoma cells were assessed. In addition, total oxidant, antioxidant status, and oxidative stress index of the cell lysates were evaluated. TNF‐α, TGF‐β, DEF‐β2, and IL‐1β inflammatory cytokine levels were also quantified enzyme‐linked immunosorbent assays. Molecular docking was used to examine the interactions between the primary phytochemicals and selected proteins, such as MARK4, Bax, Akt1, AMPK, BRAF and MEK1 which regulate cell survival and apoptosis. The extract was rich in rosmarinic acid, which was the most prominent bioactive compound. Other phenolic compounds identified included caffeic acid, luteolin‐7‐glucoside, hyperoside, hesperidin, apigenin 7‐glucoside, kaempferol, and luteolin. The extract exhibited anticancer activity with an IC 50 value of 1.25 mg/mL. Biochemical assays revealed that the extract increased inflammatory cytokine production. Docking showed that strong binding of rosmarinic acid, hesperidin, and apigenin 7‐glucoside to MARK4, Bax, Akt1, BRAF, and MEK1 may account for anticancer activity, with ADMET profiling showing more favorable pharmacokinetics and no major CYP inhibition for apigenin 7‐glucoside and rosmarinic acid. These findings support the anticancer potential of S. pisidica extract against melanoma cells.