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Alginate-Derived Oligosaccharide Inhibits Neuroinflammation and Promotes Microglial Phagocytosis of β-Amyloid

Mar Drugs. 2015 Sep 16;13(9):5828-46. doi: 10.3390/md13095828.

Abstract

Alginate from marine brown algae has been widely applied in biotechnology. In this work, the effects of alginate-derived oligosaccharide (AdO) on lipopolysaccharide (LPS)/β-amyloid (Aβ)-induced neuroinflammation and microglial phagocytosis of Aβ were studied. We found that pretreatment of BV2 microglia with AdO prior to LPS/Aβ stimulation led to a significant inhibition of production of nitric oxide (NO) and prostaglandin E₂ (PGE₂), expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and secretion of proinflammatory cytokines. We further demonstrated that AdO remarkably attenuated the LPS-activated overexpression of toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB in BV2 cells. In addition to the impressive inhibitory effect on neuroinflammation, we also found that AdO promoted the phagocytosis of Aβ through its interaction with TLR4 in microglia. Our results suggested that AdO exerted the inhibitory effect on neuroinflammation and the promotion effect on microglial phagocytosis, indicating its potential as a nutraceutical or therapeutic agent for neurodegenerative diseases, particularly Alzheimer's disease (AD).

Keywords: alginate; microglia; neuroinflammation; phagocytosis; toll-like receptor 4; β-amyloid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Inflammation / drug therapy
  • Lipopolysaccharides / toxicity
  • Microglia / drug effects*
  • Microglia / physiology
  • Nitric Oxide / metabolism
  • Oligosaccharides / chemistry*
  • Oligosaccharides / pharmacology*
  • Phagocytosis / drug effects*

Substances

  • Alginates
  • Amyloid beta-Peptides
  • Cytokines
  • Hexuronic Acids
  • Lipopolysaccharides
  • Oligosaccharides
  • Nitric Oxide
  • Glucuronic Acid
  • Dinoprostone