Fucoxanthin Attenuates Inflammation via Interferon Regulatory Factor 3 (IRF3) to Improve Sepsis

Suppression of excessive inflammatory responses improves the survival of patients with sepsis. We previously illustrated the anti-inflammatory effects of fucoxanthin (FX), a natural carotenoid isolated from brown algae; nevertheless, the underlying mechanism remains unknown. In this study, we examine the mechanism of the action of FX by targeting interferon regulatory factor 3 (IRF3) to inhibit inflammatory response. We observed that FX regulated innate immunity by inhibiting IRF3 phosphorylation in vitro. The in silico approach demonstrated a good binding mode between FX and IRF3. To examine the in vivo effects of FX, a mouse model of sepsis induced by cecal ligation and puncture (CLP) was created using both wild-type (WT) and Irf3^-/- mice. FX significantly reduced pro-inflammatory cytokine levels and reactive oxygen species production, changed the circulating immune cell composition, and increased the survival rate of the CLP-induced sepsis model. Overall, FX ameliorated sepsis by targeting IRF3 activation, providing novel insights into the therapeutic potential and molecular mechanism of action of FX in the treatment of sepsis and suggesting that it may be used clinically to improve the survival rate in mice undergoing sepsis.