Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo.
The aim of the present study was to investigate the efficacy of fucoxanthin on endotoxin-induced uveitis (EIU) in rats. The effects of fucoxanthin on endotoxin-induced leucocyte and protein infiltration, nitric oxide (NO), prostaglandin (PG)-E2 and tumour necrosis factor (TNF)-alpha concentrations in rat aqueous humour, as well as on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) protein expression in a mouse macrophage cell line (RAW 264.7 cells) were studied. EIU was induced in male Lewis rats by a footpad injection of lipopolysaccharide (LPS). Immediately after the LPS injection, either 0.1, 1 or 10mgkg(-1) of fucoxanthin was injected intravenously. The aqueous humour was collected 24hr later from both eyes, and both the number of cells infiltrating into the aqueous humour and the aqueous humour protein concentration were measured. The levels of PGE2, NO and TNF-alpha were determined by enzyme-linked immunosorbent assay. The RAW 264.7 cells were pretreated with various concentrations of fucoxanthin for 24hr and subsequently incubated with LPS for 24hr. COX-2 and iNOS protein expression was analysed by the Western blotting method. Levels of PGE2, NO and TNF-alpha production were determined. Fucoxanthin suppressed the development of EIU in a dose-dependent fashion. Treatment with fucoxanthin resulted in a reduction in PGE2, NO and TNF-alpha concentrations in the aqueous humour. The expression of COX and iNOS protein in the fucoxanthin treated RAW264.7 cells decreased significantly compared to that the LPS group. It also significantly reduced the concentration of PGE2, NO and TNF-alpha production in the medium of cells. The present result indicate fucoxanthin suppresses the inflammation of EIU by blocking the iNOS and COX-2 protein expression and its anti-inflammatory effect on eye is comparable with the effect of predinisolone used in similar doses.
Shiratori
Kenji
K
Department of Ophthalmology and Visual Sciences, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638, Japan. shiraken@med.hokudai.ac.jp
Ohgami
Kazuhiro
K
Ilieva
Iliyana
I
Jin
Xue-Hai
XH
Koyama
Yoshikazu
Y
Miyashita
Kazuo
K
Yoshida
Kazuhiko
K
Kase
Satoru
S
Ohno
Shigeaki
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003470:Culture Media; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011239:Prednisolone / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D024341:Xanthophylls / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D003470:Culture Media; D005136:Eye Proteins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D024341:Xanthophylls; C025164:fucoxanthin; D009569:Nitric Oxide; D011239:Prednisolone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone