Department of Nutritional Sciences, University of Connecticut, 27 Manter Rd., Storrs, CT, 06269, USA.
Eur J Nutr. 2021 Sep;60(6):3315-3324. doi: 10.1007/s00394-021-02509-z. Epub 2021 Feb 17.
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.
具有叶黄素类胡萝卜素特征的岩藻黄质（FCX）具有抗炎和抗氧化作用。然而，其潜在机制尚不清楚。本研究旨在阐明 FCX 及其代谢物抑制脂多糖（LPS）诱导的巨噬细胞炎症和氧化应激的机制。
在 RAW 264.7 巨噬细胞中，测定 FCX 对促炎细胞因子和抗氧化基因的 mRNA 和蛋白表达以及活性氧（ROS）积累的影响。评估 FCX 在调节磷脂酰肌醇 3-激酶（PI3K）/AKT/核 E2 相关因子 2（NRF2）轴中的作用。
FCX 显著降低 LPS 诱导的白细胞介素（IL）6、IL1b 和肿瘤坏死因子（TNF）α mRNA 丰度和 TNFα 分泌。FCX 减弱 LPS 或叔丁基过氧化物诱导的 ROS 积累，同时增加抗氧化酶的表达。此外，trolox 当量抗氧化能力测定表明 FCX 具有强大的自由基清除特性。FCX 显著增加 LPS 处理的巨噬细胞中 NRF2 的核易位，从而诱导其靶基因表达。有趣的是，PI3K 抑制剂 LY294002 显著减弱了 FCX 对 NRF2 核易位的作用，但丝裂原活化蛋白激酶抑制剂则不然。PI3K 的下游元件 AKT 的磷酸化也被 FCX 显著增加。FCX 的代谢物，如岩藻黄质醇和amarouciaxanthin A，显著减轻 LPS 诱导的 ROS 积累和促炎细胞因子表达。
FCX 通过激活 LPS 激活的巨噬细胞中的 NRF2 发挥抗炎和抗氧化作用，至少部分通过 PI3K/AKT 途径介导。
