5-Hydroxymethylfurfural Mitigates Lipopolysaccharide-Stimulated Inflammation via Suppression of MAPK, NF-κB and mTOR Activation in RAW 264.7 Cells

Molecules. 2019 Jan 13;24(2):275. doi: 10.3390/molecules24020275.

Abstract

5-Hydroxymethylfurfural (5-HMF) is found in many food products including honey, dried fruits, coffee and black garlic extracts. Here, we investigated the anti-inflammatory activity of 5-HMF and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. 5-HMF pretreatment ranging from 31.5 to 126.0 μg/mL reduced the production of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in a concentration-dependent manner in LPS-stimulated cells. Moreover, 5-HMF-pretreated cells significantly down-regulated the mRNA expression of two major inflammatory mediators, nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and suppressed the production of pro-inflammatory cytokines, as compared with the only LPS-stimulated cells. 5-HMF suppressed the phosphorylation of extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK), IκBα, NF-κB p65, the mammalian target of rapamycin (mTOR) and protein kinase B (Akt). Besides, 5-HMF was proved to inhibit NF-κB p65 translocation into nucleus to activate inflammatory gene transcription. These results suggest that 5-HMF could exert the anti-inflammatory activity in the LPS-induced inflammatory response by inhibiting the MAPK, NF-κB and Akt/mTOR pathways. Thus, 5-HMF could be considered as a therapeutic ingredient in functional foods.

Keywords: 5-hydroxymethylfurfural; Akt/mTOR; MAPK; NF-κB; RAW 264.7; inflammation; inflammatory cytokines.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Computational Biology / methods
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Furaldehyde / analogs & derivatives*
  • Furaldehyde / pharmacology
  • Gene Expression
  • Inflammation / etiology*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / immunology*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Transcription Factor RelA / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • Nitric Oxide
  • 5-hydroxymethylfurfural
  • Furaldehyde
  • TOR Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • Dinoprostone