Neuroprotective potential of isothiocyanates in an in vitro model of neuroinflammation

Inflammopharmacology. 2021 Apr;29(2):561-571. doi: 10.1007/s10787-020-00772-w. Epub 2020 Nov 16.

Abstract

Isothiocyanates (ITCs), present as glucosinolate precursors in cruciferous vegetables, have shown anti-inflammatory, antioxidant and anticarcinogenic activities. Here, we compared the effects of three different ITCs on ROS production and on the expression of matrix metalloproteinase (MMP)-2 and -9, which represent important pathogenetic factors of various neurological diseases. Primary cultures of rat astrocytes were activated by LPS and simultaneously treated with different doses of Allyl isothiocyanate (AITC), 2-Phenethyl isothiocyanate (PEITC) and 2-Sulforaphane (SFN). Results showed that SFN and PEITC were able to counteract ROS production induced by H2O2. The zymographic analysis of cell culture supernatants evidenced that PEITC and SFN were the most effective inhibitors of MMP-9, whereas, only SFN significantly inhibited MMP-2 activity. PCR analysis showed that all the ITCs used significantly inhibited both MMP-2 and MMP-9 expression. The investigation on the mitogen-activated protein kinase (MAPK) signaling pathway demonstrated that ITCs modulate MMP transcription by inhibition of extracellular-regulated protein kinase (ERK) activity. Results of this study suggest that ITCs could be promising nutraceutical agents for the prevention and complementary treatment of neurological diseases associated with MMP involvement.

Keywords: Anti-inflammatory; Antioxidant; Isothiocyanate; Matrix metalloproteinases; Neurodegenerative diseases.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Cells, Cultured
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Isothiocyanates / administration & dosage
  • Isothiocyanates / pharmacology*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Sulfoxides / administration & dosage
  • Sulfoxides / pharmacology*

Substances

  • Isothiocyanates
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Sulfoxides
  • phenethyl isothiocyanate
  • allyl isothiocyanate
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • sulforaphane