Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling

Int J Mol Sci. 2017 Jul 3;18(7):1423. doi: 10.3390/ijms18071423.


Allyl isothiocyanate (AITC), present in Wasabia japonica (wasabi), is an aliphatic isothiocyanate derived from the precursor sinigrin, which is a glucosinolate present in vegetables of the Brassica family. Traditionally, it has been used to treat rheumatic arthralgia, blood circulation, and pain. This study focuses on its anti-apoptotic activity through the regulation of lipopolysaccharide (LPS)-induced neuroinflammation. Furthermore, we assessed its neuroprotective efficacy, which it achieves through the upregulation of nerve growth factor (NGF) production. Pretreatment with AITC significantly inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) production in activated microglia, and increased the nerve growth factor (NGF) and neurite outgrowth in neuroblastoma cells. AITC inhibited the nuclear factor (NF-κB-mediated transcription by modulating mitogen activated protein kinase (MAPK) signaling, particularly downregulating c-Jun N-terminal kinase (JNK) phosphorylation, which was followed by a reduction in the TNF-α expression in activated microglia. This promising effect of AITC in controlling JNK/NF-κB/TNF-α cross-linking maintains the Bcl-2 gene family and protects neuroblastoma cells from activated microglia-induced toxicity. These findings provide novel insights into the anti-neuroinflammatory effects of AITC on microglial cells, which may have clinical significance in neurodegeneration.

Keywords: allyl isothiocyanate; astrocyte; microglia; neuroinflammation; neuron; neuroprotection.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Coumaric Acids / pharmacology
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Inflammation Mediators / metabolism
  • Isothiocyanates / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Microglia / drug effects
  • Microglia / metabolism
  • NF-kappa B / metabolism*
  • Nerve Growth Factor / metabolism
  • Neurites / drug effects
  • Neurites / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neurotoxins / toxicity
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / pharmacology
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism*


  • Anti-Inflammatory Agents
  • Coumaric Acids
  • Inflammation Mediators
  • Isothiocyanates
  • Lipopolysaccharides
  • NF-kappa B
  • Neuroprotective Agents
  • Neurotoxins
  • Plant Extracts
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • sinapinic acid
  • Nerve Growth Factor
  • allyl isothiocyanate
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • JNK Mitogen-Activated Protein Kinases
  • Dinoprostone