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

Area of Science:

• Pharmacology
• Molecular Biology
• Oncology

Background:

• Schisandrin B (Sch B), from Schisandra chinensis, shows anti-tumor effects on cholangiocarcinoma (CCA).
• The precise molecular mechanisms underlying Sch B's anti-CCA activity require further investigation.

Purpose of the Study:

• To elucidate the molecular mechanism of Sch B against CCA.
• To investigate the role of the reactive oxygen species (ROS)/p38MAPK/NF-κB signaling axis in Sch B's action.

Main Methods:

• Integrated network pharmacology for target prediction and molecular docking for binding affinity.
• In vitro experiments to validate computational findings and assess cellular effects.
• Analysis of ROS levels, cell proliferation, apoptosis, and key signaling pathway components (p38 MAPK, NF-κB).

Main Results:

• Sch B targets were enriched in cancer and MAPK signaling pathways, with strong binding to MAPK1.
• Sch B dose-dependently increased ROS, suppressed CCA cell proliferation, and induced apoptosis.
• Sch B inhibited p38 MAPK and NF-κB pathways, reducing pro-inflammatory cytokines (IL-6, IL-8, TNF-α).

Conclusions:

• Sch B exerts anti-CCA effects via ROS-mediated regulation of p38MAPK and NF-κB pathways.
• Sch B demonstrates potential as a multi-target natural therapeutic agent for CCA.
• Findings provide a foundation for further development of Sch B for CCA treatment.