6,6-Bieckol suppresses inflammatory responses by down-regulating nuclear factor-B activation via Akt, JNK, and p38 MAPK in LPS-stimulated microglial cells

초록

Objective: Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the pharmaceutical properties of 6,6-bieckol on the regulation of nuclear factor-B (NF-B) activation responsible to the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 using lipopolysaccharide (LPS)-stimulated BV2 and murine primary microglial cells.Meterials and methods: The levels of nitric oxide (NO), prostaglandin E-2 (PGE)(2), and pro-inflammatory cytokines were measured by Griess assay and enzyme-linked immunosorbent assay. The levels of iNOS, COX-2, mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of NF-B were determined by immunofluorescence and reporter gene assay, respectively.Results: We found that 6,6-bieckol decreased the expression of iNOS and COX-2 as well as pro-inflammatory cytokines in LPS-stimulated BV2 and primary microglial cells in a dose-dependent manner. 6,6-Bieckol inhibited activation of NF-B by preventing the degradation of inhibitor B (IB)- and led to prevent the nuclear translocation of NF-B/p65 subunit. Moreover, 6,6-bieckol inhibited the phosphorylation of Akt, JNK, and p38 MAPK.Discussion and conclusion: These results indicate that the anti-inflammatory effect of 6,6-bieckol on LPS-stimulated microglial cells is mainly regulated by the inhibition of IB-/NF-B and JNK/p38 MAPK/Akt pathways, supporting biochemical characteristics of the compound for therapeutic agent against neuroinflammatory diseases caused by microglial activation.

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