Inhibition of HMGB1/TLR4 signaling pathway by Schisandrin in RAW264.7 murine macrophages

Schisandrin is one of the main components isolated from Schisandra fruit (Schisandra chinesnesis) and has been prescribed for hepatitis treatment. Recent studies have demonstrated that Schisandrin shows anti-inflammation, anti-oxidative and anti-allergic effects in vivo and in vitro models. However, the fundamental mechanism of anti-inflammation by Schisandras has not been fully evaluated. Here, we aimed to study the anti-inflammatory role through the modulation of High mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway by Schisandrin. Schisandrin inhibited HMGB1 expression and translocation, reduced HMGB1/TLR4 binding and lipid raft recruitment, and suppressed the activation of Nuclear Factor-kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) pathways. These effects led to a concentration-dependent reduction in LPS-induced inflammation, suggesting that Schisandrin attenuates inflammation by modulating HMGB1/TLR4-mediated signaling. These findings provide novel insights into the molecular basis of Schisandrin's anti-inflammatory activity and highlight its potential as a therapeutic agent for HMGB1/TLR4-associated inflammatory diseases.