NF-kB Regulation and MAPKs activation of lipopolysaccharide-induced RAW 264.7 macrophages by fucoxanthin from Ishige okamurae

Abstract

It is well known that pro-inflammatory mediators like nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) contribute to the courses of many inflammatory diseases. In the present study, the authors investigated the anti-inflammatory effects of fucoxanthin, a natural biologically active substance isolated from Ishige okamurae by examining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Fucoxanthin caused dose-dependent reductions in the levels of inducible nitric oxide (iNOS) at protein and mRNA levels and concomitant decreases in NO production. In addition, it was found that fucoxanthin suppressed the production and mRNA expressions of inflammatory cytokines, such as, IL-1β, TNF-α and IL-6. Furthermore, molecular data revealed that fucoxanthin inhibited the LPS-stimulated DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-κB). Moreover, this effect was accompanied by decreases in the phosphorylation of inhibitory κB (IκB)-α and in the subsequent blocking of p65 subunit of NF-κB translocation to the nucleus. In addition, fucoxanthin dose-dependently inhibited the phosphorylations of JNK, ERK and p38. Taken together, these results suggest that fucoxanthin reduces levels of the pro-inflammatory mediators, such as, iNOS, IL-1β, TNF-α, and IL-6 through the inhibition of NF-κB activation via the suppression of JNK, ERK and p38 phosphorylation in RAW 264.7 cells. These findings reveal in part the molecular basis for the anti-inflammatory properties of fucoxanthin.