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

Suppression of excessive inflammatory responses improvesthe survivalof patients with sepsis. We previously illustrated the anti-inflammatoryeffects of fucoxanthin (FX), a natural carotenoid isolated from brownalgae; nevertheless, the underlying mechanism remains unknown. Inthis study, we examine the mechanism of the action of FX by targetinginterferon 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 demonstrateda good binding mode between FX and IRF3. To examine the invivo effects of FX, a mouse model of sepsis induced by cecalligation and puncture (CLP) was created using both wild-type (WT)and Irf3(-/-) mice. FX significantlyreduced pro-inflammatory cytokine levels and reactive oxygen speciesproduction, changed the circulating immune cell composition, and increasedthe survival rate of the CLP-induced sepsis model. Overall, FX amelioratedsepsis by targeting IRF3 activation, providing novel insights intothe therapeutic potential and molecular mechanism of action of FXin the treatment of sepsis and suggesting that it may be used clinicallyto improve the survival rate in mice undergoing sepsis.

Automated summary

Suppression of excessive inflammatory responses improves the survival of patients with sepsis. This study investigates the mechanism of action of fucoxanthin (FX), a natural carotenoid, in inhibiting inflammatory response by targeting interferon regulatory factor 3 (IRF3). In vitro experiments show that FX inhibits IRF3 phosphorylation, while in vivo experiments demonstrate that FX reduces pro-inflammatory cytokine levels, changes immune cell composition, and increases the survival rate in a sepsis mouse model. Overall, FX ameliorates sepsis by targeting IRF3 activation, providing novel insights into its therapeutic potential and molecular mechanism of action.