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.