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Neurochem Res. 2017 Feb;42(2):667-677. doi: 10.1007/s11064-016-2123-6. Epub 2016 Dec 8.

Anti-Neuroinflammatory Effects of Fucoxanthin via Inhibition of Akt/NF-κB and MAPKs/AP-1 Pathways and Activation of PKA/CREB Pathway in Lipopolysaccharide-Activated BV-2 Microglial Cells.

Author information

1
Natural Product Research Center, KIST Gangneung Institute of Natural Products, Gangneung, 210-340, Republic of Korea.
2
Department of Biological Chemistry, Korea University of Science and Technology (UST), Daejeon, 305-333, Republic of Korea.
3
Natural Product Research Center, KIST Gangneung Institute of Natural Products, Gangneung, 210-340, Republic of Korea. hoyang@kist.re.kr.
4
Department of Biological Chemistry, Korea University of Science and Technology (UST), Daejeon, 305-333, Republic of Korea. hoyang@kist.re.kr.

Abstract

Microglia play a critical role in controlling the homeostasis of the brain, but over-activated microglia secrete pro-inflammatory mediators and cytokines, which induce neuronal cell death. Fucoxanthin (Fx), a marine carotenoid, has demonstrated a variety of beneficial health effects. Despite accumulating evidence supporting the immune-modulating effects of Fx in vitro, the underlying signaling pathways remain unknown. In the present study, Fx dose-dependently inhibited the secretion of lipopolysaccharide (LPS)-induced pro-inflammatory mediators including interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), prostaglandin (PG) E2, and nitric oxide (NO) productions, and also suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzymes. Further, the reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated IL-6, TNF-α, iNOS, and COX-2 mRNA expression were suppressed by treatment with Fx in a dose-dependently manner. The mechanism studies indicated that Fx blocks protein kinase B (Akt)/nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPKs)/transcription factor (AP)-1 pathways. In addition, we demonstrated that Fx increases nuclear factor erythroid 2-related factor (Nrf)-2 activation and heme oxygenase (HO)-1 expression in LPS-activated BV-2 microglia. Subsequently, we found that Fx also mediates the reactive oxygen species (ROS) by activating protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) pathway, and promotes the production of brain-derived neurotrophic factor (BDNF). These results indicate that Fx may be more effective and potential than other candidates via either decreasing the pro-inflammatory factors production or increasing the neuroprotective molecules expression for therapy of neurodegenerative diseases.

KEYWORDS:

BV-2 microglia; Fucoxanthin; Neuro-inflammation; PKA/CREB pathway

PMID:
27933547
DOI:
10.1007/s11064-016-2123-6
[Indexed for MEDLINE]

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