Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice

Exp Neurol. 2013 Dec;250:239-49. doi: 10.1016/j.expneurol.2013.10.002. Epub 2013 Oct 9.

Abstract

Sulforaphane (SFN) is an organosulfur compound present in vegetables and has potent anti-oxidant and anti-inflammatory activities. This study was aimed at investigating the effect of treatment with SFN on inflammation and oxidative stress, and the potential mechanisms underlying the action of SFN in experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. Treatment with SFN significantly inhibited the development and severity of EAE in mice, accompanied by mitigating inflammatory infiltration and demyelination in the spinal cord of mice. The protective effect of SFN was associated with significantly improved distribution of claudin-5 and occludin, and decreased levels of MMP-9 expression, preserving the blood-brain barrier. Furthermore, the protection of SFN was also related to decreased levels of oxidative stress in the brains of mice by enhanced activation of the Nrf2/ARE pathway and increased levels of anti-oxidant HO-1 and NQO1 expression. In addition, treatment with SFN inhibited antigen-specific Th17 responses and enhanced IL-10 responses. Our data indicated that treatment with SFN inhibited EAE development and severity in mice by its anti-oxidant activity and antagonizing autoimmune inflammation. Our findings suggest that SFN and its analogues may be promising reagents for intervention of multiple sclerosis and other autoimmune diseases.

Keywords: Experimental autoimmune encephalomyelitis; Inflammation; Multiple sclerosis; Nrf2; Oxidative stress; Sulforaphane; Th17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Immunohistochemistry
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / pathology
  • Isothiocyanates / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Oxidative Stress / drug effects*
  • Real-Time Polymerase Chain Reaction
  • Spinal Cord / drug effects
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology*

Substances

  • Antioxidants
  • Isothiocyanates
  • sulforafan