Protective Effects of 6-(Methylsulfinyl)hexyl Isothiocyanate on Aβ 1-42-Induced Cognitive Deficit, Oxidative Stress, Inflammation, and Apoptosis in Mice

Int J Mol Sci. 2018 Jul 18;19(7):2083. doi: 10.3390/ijms19072083.

Abstract

Alzheimer's disease (AD) is the most common form of dementia among older people. Although soluble amyloid species are recognized triggers of the disease, no therapeutic approach is able to stop it. 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in Wasabia japonica, which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties. The aim of the present study was to investigate the neuroprotective activity of 6-MSITC in a murine AD model, induced by intracerebroventricular injection of β-amyloid oligomers (Aβ1-42O). The treatment with 6-MSITC started 1 h after the surgery for the next 10 days. Behavioral analysis showed that 6-MSITC ameliorated Aβ1-42O-induced memory impairments. The decrease of glutathione levels and increase of reactive oxygen species in hippocampal tissues following Aβ1-42O injection were reduced by 6-MSITC. Moreover, activation of caspases, increase of inflammatory factors, and phosphorylation of ERK and GSK3 were inhibited by 6-MSITC. These results highlighted an interesting neuroprotective activity of 6-MSITC, which was able to restore a physiological oxidative status, interfere positively with Nrf2-pathway, decrease apoptosis and neuroinflammation and contribute to behavioral recovery. Taken together, these findings demonstrated that 6-MSITC could be a promising complement for AD therapy.

Keywords: 6-(methylsulfinyl)hexyl isothiocyanate; Alzheimer’s disease; Aβ oligomers; neuroinflammation; neuroprotection; oxidative stress.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Apoptosis* / drug effects
  • Caspases / metabolism
  • Cell Death / drug effects
  • Cognition Disorders / complications
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / pathology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology
  • Isothiocyanates / therapeutic use*
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidation-Reduction
  • Oxidative Stress* / drug effects
  • Phosphorylation / drug effects

Substances

  • 6-(Methylsulfinyl)hexyl isothiocyanate
  • Amyloid beta-Peptides
  • Isothiocyanates
  • Neuroprotective Agents
  • Glycogen Synthase Kinase 3 beta
  • Extracellular Signal-Regulated MAP Kinases
  • Caspases