Schisandrin B suppresses cholangiocarcinoma by targeting the ROS/p38 MAPK/NF-κB axis.

Schisandrin B (Sch B), a bioactive component isolated from the traditional Chinese medicine Schisandra chinensis, exhibits anti-tumor activity against cholangiocarcinoma (CCA), though its complete molecular mechanism remains to be fully elucidated. The present study employed an integrated strategy combining network pharmacology for target prediction, molecular docking for binding affinity validation and comprehensive in vitro experiments to investigate the regulation of the reactive oxygen species (ROS)/p38MAPK/NF-κB signaling axis by Sch B. Computational analyses revealed significant enrichment of Sch B targets in cancer-related pathways and MAPK signaling, while molecular docking confirmed strong binding to core targets including MAPK1. Experimental validation demonstrated that Sch B dose-dependently elevated intracellular ROS levels, resulting in suppressed proliferation and induced apoptosis in CCA cells, effects reversible by the ROS scavenger N-acetyl-L-cysteine. Mechanistic studies further identified that Sch B concurrently inhibits p38 MAPK signaling through reduced phosphorylated-p38 and AP-1 expression, and suppresses NF-κB pathway activation by impeding p65 nuclear translocation, leading to diminished release of pro-inflammatory cytokines IL-6, IL-8 and TNF-α. These findings collectively establish that Sch B exerts its anti-CCA effects through ROS-mediated coordinated regulation of both p38MAPK and NF-κB pathways, underscoring its potential as a multi-target natural therapeutic agent for CCA treatment and providing a solid foundation for further development.