Euryfuranyl compounds from edible species of cuttlefish as potential anti-inflammatory leads attenuating NF-κB signaling cascade in lipopolysaccharide-activated macrophages

Nuclear factor-kappa B is an inducible transcription element, which was considered as an important regulator of immune functions, and plays a critical role to induce inflammatory reactions. In this study, we have demonstrated the anti-inflammatory potentials of previously undescribed (4 -> 13)-abeo-euryfuranyls (1-2) from the spineless cuttlefish Sepiella inermis in lipopolysaccharide-stimulated macrophages. The euryfuranyl bearing (4 -> 13)-abeo-euryfuranyl-2-ene-6-hydroxymethyl-propanoate framework (compound 1) displayed prominent inhibitory effects against pro-inflammatory cyclooxygenase-2 (IC50 0.36 mM) and 5-lipoxygenase (IC50 0.70 mM). Additionally, it suppressed the generation of inducible nitric oxide synthase along with cyclooxygenase-2 and 5-lipoxygenase in lipopolysaccharide-stimulated macrophages. The euryfuranyl analogue (1) down-regulated the mRNA expression of cyclooxygenase-2 and nuclear factor-.B signaling pathway in lipopolysaccharide-activated macrophage cells by hindering the degradation of inhibitor-kappa B proteins, and transfer of the subunit NF-kappa B p(65) to the nucleus from the cytosol. These results demonstrated that the euryfuranyl analogue could be explored as a promising anti-inflammatory therapeutic lead attenuating nuclear factor-kappa B signaling cascade.