The Anti-Inflammatory Effects Of Fucoxanthin And Its Regulation In Innate Immune Response

Carotenoid family compounds,derived from marine plants,are the important resources for the food and pharmaceutical industries,and have a profound impact on human health.In the era of vigorous development of marine resources,the study of the functions of carotenoids will advance our understanding of marine resources and have great significance for the industrial development.Fucoxanthin（FX）is a rich carotenoid with high yield in the marine resources.Therefore,it would be interested to explore its unknown functions in terms of its potential pharmaceutical applications.In this dissertation,we studied its anti-inflammatory effects and explored the underlying mechanism.Lipopolysaccharide（LPS）was used as a stimulator to induce the release of inflammatory cytokines in Raw264.7 cells.By detecting the expression level of inflammatory cytokines in cells,it was shown that FX could suppress the mRNA expression of pro-inflammatory cytokines in Raw264.7 cells.By using enzyme-linked immunosorbent assay（ELISA）and immunoblotting,it was shown that FX could down-regulate selected pro-inflammatory cytokine protein expression.Luciferase fluorescence chromogenic assay was used to determine the effect of FX inhibiting the activation of NF-κB in THP1-Lucia/NFκB cells,and the EC₅₀0 for inhibiting NF-κB activation was 3.78μM.Subsequently,the anti-inflammatory effects of FX in vivo were tested on an sepsis mouse model.In the LPS-induced sepsis model,FX significantly improved the survival of mice.The FX effect on survival was better than the clinical emergency drug Urinastatin（UST）.Compared with the positive model group mice,FX effectively reduced the expression level of pro-inflammatory cytokines in the liver of sepsis model mice,and down-regulated the expression of pro-inflammatory cytokine protein in serum as well.HE staining showed that the treatment of FX had obvious protective effects on the liver.NF-κB serves as a convergent point for multiple immune pathway signals.FX had a function of inhibiting NF-κB activation,suggesting its functions in regulating immune signaling.Since FX had effects on NF-?B and NF-?B can be activated by cGAS-STING-mediated immune activation,we further tested the FX effects on this pathway.In L929 cells,FX effectively down-regulated type I interferon mediated by cGAS and STING activation.We also tested the FX effects on the key proteins TBK1 and IRF3 in the cGAS-STING pathwayby immunoblotting.The data showed that FX could significantly inhibit the IRF3 dimerization and decreased its phosphorylation,suggesting the inhibitory effect of FX on IRF3 function.In summary,we demonstrated the anti-inflammatoryeffects of FX in both cell lines and animal models.These effects were correlated to the improved survival rate in mouse sepsis model.