6,6′-Bieckol, isolated from marine alga Ecklonia cava, suppressed LPS-induced nitric oxide and PGE ₂ production and inflammatory cytokine expression in macrophages: The inhibition of NFκB

Ecklonia cava is an edible brown alga that contains high levels of phlorotannins, which are unique marine polyphenolic compounds. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of phlorotannin 6,6′-bieckol, which is an active component isolated from E. cava, on lipopolysaccharide (LPS)-stimulated primary macrophages and RAW 264.7 macrophage cells. 6,6′-Bieckol was found to inhibit nitric oxide (NO) and prostaglandin E ₂ (PGE ₂) production and to suppress the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, 6,6′-bieckol downregulated the production and mRNA expression of the inflammatory cytokines TNF-α and IL-6. Moreover, pretreatment with 6,6′-bieckol decreased LPS-induced transactivation of nuclear factor-kappa B (NFκB) and nuclear translocation of p50 and p65 subunits of NFκB. Furthermore, chromatin immunoprecipitation assay revealed that 6,6′-bieckol inhibited LPS-induced NFκB binding to the TNF-α and IL-6 promoters. Taken together, these data suggest that the anti-inflammatory properties of 6,6′-bieckol are related to the down-regulation of iNOS, COX-2, and pro-inflammatory cytokines through the negative regulation of the NFκB pathway in LPS-stimulated macrophages.