Bioactive components of Schisandra chinensis and their mechanisms in enhancing chemosensitivity of ovarian cancer

Schisandra chinensis extract (SCE) sensitizes SKOV3 cells to doxorubicin. • UPLC-Q-TOF/MS identifies 247 components; 25 bioactive candidates are screened by network pharmacology. • SCE, not single lignans, co-inhibits PI3K-AKT, MAPK and STAT3 pathways. • SCE suppresses ovarian cancer cell migration and invasion. • SCE's multi-target synergy supports its use as a chemotherapy adjuvant. Despite the documented potential of Schisandra chinensis extract (SCE) in enhancing chemosensitivity and providing hepatorenal protection, its active components and underlying mechanisms remain unclear. Herein, this study systematically identifies the bioactive components of SCE and elucidates their role in sensitizing ovarian cancer (OC) cells. The 80% ethanol fraction, prepared by macroporous resin column chromatography, demonstrated potent chemosensitizing activity. UPLC-Q-TOF/MS analysis identifies 247 compounds, from which network pharmacology screening yielded 25 potential active molecules and 7 key protein targets. Molecular docking reveals strong binding of schisandrin C and schizandrol B to PI3K and MAPK3. Western blot analysis further confirms the superior inhibitory effect of SCE over its individual constituents on PI3K-AKT, MAPK, and STAT3 pathways, highlighting a synergistic mechanism that underlies the enhanced chemosensitivity. Furthermore, scratch assay, migration, and invasion assays collectively confirm the anti-metastatic potential of SCE. This study deciphers the multi-target mechanism of S. chinensis in enhancing chemosensitivity of OC, providing both mechanistic insights for drug development and a foundation for integrative medicine. Download: Download high-res image (231KB) Download: Download full-size image