The flavonoid-enriched fraction AF4 suppresses neuroinflammation and promotes restorative gene expression in a mouse model of experimental autoimmune encephalomyelitis

J Neuroimmunol. 2014 Mar 15;268(1-2):71-83. doi: 10.1016/j.jneuroim.2014.01.007. Epub 2014 Jan 21.

Abstract

The anti-inflammatory and restorative effects of the flavonoid-enriched fraction AF4 were examined in a mouse model of experimental autoimmune encephalomyelitis (EAE). Relative to EAE mice that received vehicle (water, 10 ml/kg/day), oral administration of AF4 (25mg/kg/day) beginning 24h after the onset of clinical signs reduced disease severity from days 19-31 post-immunization. AF4-mediated recovery from EAE was preceded by reduced plasma concentrations of TNFα and IL-1β on day 18 followed by decreased cytokine production and neuropathology in the cerebellum and spinal cord on day 31. Clinical improvement for EAE-AF4 mice from days 18 to 31 was accompanied by the elevated expression of genes that mediate remyelination. These findings suggest that AF4 decreased EAE severity by promoting the resolution of inflammation and improving functional recovery in the CNS.

Keywords: Chemokine; Cytokine; Multiple sclerosis; Polyphenolic; Remyelination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Brain / drug effects
  • Brain / immunology
  • Brain / pathology
  • Chromatography, Liquid
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flavonoids / pharmacology*
  • Gene Expression / drug effects*
  • Immunohistochemistry
  • Malus / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spinal Cord / drug effects
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • Tandem Mass Spectrometry

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Flavonoids
  • Plant Extracts