Anti-inflammatory effects of fucoidan through inhibition of NF-κB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells

Food Chem Toxicol. 2011 Aug;49(8):1745-52. doi: 10.1016/j.fct.2011.04.020. Epub 2011 May 4.

Abstract

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, displays a wide variety of internal biological activities; however, the cellular and molecular mechanisms underlying fucoidan's anti-inflammatory activity remain poorly understood. In this study, we investigated the inhibitory effects of fucoidan on production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators in BV2 microglia. Our data indicated that fucoidan treatment significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) in LPS-stimulated BV2 microglia. It also attenuated expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, monocyte chemoattractant protein-1 (MCP-1), and pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α. Moreover, fucoidan exhibited anti-inflammatory properties by suppression of nuclear factor-kappa B (NF-κB) activation and down-regulation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and AKT pathways. These finding suggest that fucoidan may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / metabolism
  • Down-Regulation
  • Fucus / chemistry
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / adverse effects
  • Mice
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / pharmacology
  • Polysaccharides / pharmacology*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rabbits
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Chemokine CCL2
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Polysaccharides
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • fucoidan
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Dinoprostone