Neoagaro-oligosaccharide monomers inhibit inflammation in LPS-stimulated macrophages through suppression of MAPK and NF-κB pathways

Sci Rep. 2017 Mar 7:7:44252. doi: 10.1038/srep44252.

Abstract

Neoagaro-oligosaccharides derived from agarose have been demonstrated to possess a variety of biological activities, such as anti-bacteria and anti-oxidative activities. In this study, we mainly explored the inhibitory effects and the mechanisms of neoagaro-oligosaccharide monomers against LPS-induced inflammatory responses in mouse macrophage RAW264.7 cells. The results indicated that neoagaro-oligosaccharide monomers especially neoagarotetraose could significantly reduce the production and release of NO in LPS-induced macrophages. Neoagarotetraose significantly suppressed the expression and secretion of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines such as TNF-α and IL-6. The inhibition mechanisms may be associated with the inhibition of the activation of p38MAPK, Ras/MEK/ERK and NF-κB signaling pathways. Thus, neoagarotetraose may attenuate the inflammatory responses through downregulating the MAPK and NF-κB signaling pathways in LPS-stimulated macrophages. In summary, the marine-derived neoagaro-oligosaccharide monomers merit further investigation as novel anti-inflammation agents in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Carbohydrate Sequence
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Galactosides / pharmacology*
  • Gene Expression Regulation
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / antagonists & inhibitors*
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Oligosaccharides / pharmacology*
  • RAW 264.7 Cells
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Anti-Inflammatory Agents
  • Galactosides
  • IL6 protein, human
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Oligosaccharides
  • Tumor Necrosis Factor-alpha
  • neoagarotetraose
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • ras Proteins