Fucoxanthin inhibits lipopolysaccharide-induced inflammation and oxidative stress by activating nuclear factor E2-related factor 2 via the phosphatidylinositol 3-kinase/AKT pathway in macrophages



Anti-inflammatory and antioxidant effects of fucoxanthin (FCX), a xanthophyll carotenoid, have been suggested. However, underlying mechanisms are elusive. The objective of this study was to elucidate the mechanisms by which FCX and its metabolites inhibit lipopolysaccharide (LPS)-induced inflammation and oxidative stress in macrophages.


The effects of the FCX on mRNA and protein expression of pro-inflammatory cytokines and antioxidant genes, and reactive oxygen species (ROS) accumulation were determined in RAW 264.7 macrophages. A potential role of FCX in the modulation of phosphatidylinositol 3-kinase (PI3K)/AKT/nuclear E2-related factor 2 (NRF2) axis was evaluated.


FCX significantly decreased LPS-induced interleukin (Il)6, Il1b, and tumor necrosis factor α (Tnf) mRNA abundance and TNFα secretion. FCX attenuated LPS or tert-butyl-hydroperoxide-induced ROS accumulation with concomitant increases in the expression of antioxidant enzymes. Also, trolox equivalent antioxidant capacity assay demonstrated that FCX had a potent free radical scavenging property. FCX markedly increased nuclear translocation of NRF2 in LPS-treated macrophages, consequently inducing its target gene expression. Interestingly, the effect of FCX on NRF2 nuclear translocation was noticeably diminished by LY294002, an inhibitor of PI3K, but not by inhibitors of mitogen-activated protein kinases. Phosphorylation of AKT, a downstream element of PI3K, was also markedly increased by FCX. FCX metabolites, such as fucoxanthinol and amarouciaxanthin A, significantly attenuated LPS-induced ROS accumulation and pro-inflammatory cytokine expression.


FCX exerts anti-inflammatory and antioxidant effects by the activation of NRF2 in the macrophages activated by LPS, which is mediated, at least in part, through the PI3K/AKT pathway.

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2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)


Amarouciaxanthin A


Antioxidant response element


Bone marrow-derived macrophages








Focal adhesion kinase


Glutathione peroxidase 1


Heme oxygenase-1






Kelch-like ECH-associated protein 1




Mitogen-activated protein kinases


Nuclear factor κB


Nuclear E2-related factor 2


Phosphatidylinositol 3-kinase


Reactive oxygen species


Superoxide dismutase 1


Total antioxidant capacity




Trolox equivalent antioxidant capacity


Tumor necrosis factor α


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This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1A6A3A03032678) to M-.B. Kim and by funds from the College of Agriculture, Health and Natural Resources at the University of Connecticut to J-.Y. Lee.

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MBK: conducted experiments, analyzed data, and wrote the manuscript. HK, YL, and YKP: performed experiments and contributed to manuscript preparation. JYL: designed the study, directed the study, interpreted data, and contributed to manuscript preparation.

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Correspondence to Ji-Young Lee.

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Kim, MB., Kang, H., Li, Y. et al. Fucoxanthin inhibits lipopolysaccharide-induced inflammation and oxidative stress by activating nuclear factor E2-related factor 2 via the phosphatidylinositol 3-kinase/AKT pathway in macrophages. Eur J Nutr (2021). https://doi.org/10.1007/s00394-021-02509-z

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  • Fucoxanthin
  • Xanthophyll
  • Inflammation
  • Oxidative stress
  • NRF2
  • PI3K
  • Macrophages