Phytochemical Characterization and Cytotoxic Potential of the Ethyl Acetate Fraction of Schima superba Bark: An In Vitro and In Silico Investigation

Natural products represent a valuable source of anticancer agents, although their mechanisms of action are often incompletely understood. In this study, we evaluated the cytotoxic effects of the ethyl acetate (EA) fraction derived from Schima superba bark. The EA fraction exhibited selective cytotoxicity against HepG2 and MCF-7 cancer cells, with minimal effects on normal HEK293 cells, and induced apoptosis as evidenced by time- and dose-dependent activation of caspase-3. Phytochemical profiling by UPLC-QTOF-MS/MS identified 18 major constituents, predominantly phenylethanoid glycosides and triterpenoids. To gain insight into the underlying mechanism, molecular docking, 200 ns molecular dynamics simulations, and MM-PBSA analyses were performed targeting poly (ADP-ribose) polymerase 1 (PARP1) and caspase-3. Among the identified compounds, cistanoside D displayed favorable binding affinity toward both targets, but formed a more stable and energetically favorable complex with PARP1 during molecular dynamics simulations, whereas its interaction with caspase-3 was comparatively weak. These findings suggest that cistanoside D may preferentially interact with PARP1, while the observed activation of caspase-3 is likely associated with downstream apoptotic processes rather than direct enzymatic modulation. This study provides an integrated evaluation of the phytochemical composition and anticancer potential of Schima superba bark extract, and identifies cistanoside D as a promising candidate for further investigation. These results contribute to a better understanding of the molecular basis underlying the bioactivity of this medicinal plant and support its potential as a source of anticancer agents.