Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-κB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages.
It has been previously determined that pro-inflammatory mediators including nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β and IL-6 contribute to the courses of a variety of inflammatory diseases. In this study, we evaluated the anti-inflammatory effects of fucoxanthin (FX), a natural biologically active substance isolated from Ishige okamurae, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. FX induced dose-dependent reductions in the levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and concomitant reductions in the production of NO and PGE₂. Additionally, FX was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, FX inhibited the cytoplasmic degradation of inhibitors of B (IκB)-α and the nuclear translocation of p50 and p65 proteins, resulting in lower levels of nuclear factor (NF)-κB transactivation. Additionally, FX was shown to induce a dose-dependent inhibition of the phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK and p38). Collectively, the results of this study demonstrate that FX reduces the levels of pro-inflammatory mediators including NO, PGE₂, IL-1β, TNF-α, and IL-6 via the inhibition of NF-κB activation and the suppression of MAPK phosphorylation in RAW 264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of FX.
Kim
Kil-Nam
KN
Jeju Biodiversity Research Institute (JBRI) and Jeju Hi-Tech Industry Development Institute (HiDI), Jeju 697-943, Republic of Korea.
Heo
Soo-Jin
SJ
Yoon
Weon-Jong
WJ
Kang
Sung-Myung
SM
Ahn
Ginnae
G
Yi
Tae-Hoo
TH
Jeon
You-Jin
YJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009994:Osmolar Concentration; D000459:Phaeophyceae / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D024341:Xanthophylls / Q000302:isolation & purification / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D024341:Xanthophylls; C025164:fucoxanthin; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone