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.


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


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