The Isothiocyanate Isolated from Moringa oleifera Shows Potent Anti-Inflammatory Activity in the Treatment of Murine Subacute Parkinson's Disease

Rejuvenation Res. 2017 Feb;20(1):50-63. doi: 10.1089/rej.2016.1828. Epub 2016 Jun 24.

Abstract

The present study was aimed at estimating a possible neuroprotective effect of glucomoringin (GMG) [4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate] bioactivated with the enzyme myrosinase to form the corresponding isothiocyanate [4-(α-L-rhamnopyranosyloxy)benzyl C; moringin] in the treatment or prevention of Parkinson's disease (PD). In this study, the beneficial effects of moringin were compared with those of pure GMG, not enzymatically activated, in an in vivo experimental mouse model of subacute PD. Subacute PD was induced in C57BL/6 mice by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were pretreated daily for 1 week with moringin (10 mg/kg +5 μL myrosinase/mouse) and with GMG (10 mg/kg). Behavioral evaluations were also performed to assess motor deficits and bradykinesia in MPTP mice. Besides, assuming that pretreatment with moringin could modulate the triggering of inflammatory cascade with a correlated response, we tested its in vitro anti-inflammatory activity by using a model of RAW 264.7 macrophages stimulated with lipopolysaccharide. Achieved results in vivo showed a higher efficacy of moringin compared with GMG not only to modulate the inflammatory pathway but also oxidative stress and apoptotic pathways. In addition, the greater effectiveness of moringin in countering mainly the inflammatory pathway has been corroborated by the results obtained in vitro. The relevance and innovation of the present study lie in the possible use of a safe formulation of a bioactive compound, resulting from exogenous myrosinase hydrolysis of the natural phytochemical GMG, which can be used in clinical practice as a useful drug for the treatment or prevention of PD.

Keywords: MPTP experimental model; RAW 264.7 macrophages; glucosinolates; proinflammatory cytokines.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Biomarkers / metabolism
  • Body Weight / drug effects
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Inflammation / pathology
  • Isothiocyanates / pharmacology
  • Isothiocyanates / therapeutic use*
  • Lipopolysaccharides
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Moringa oleifera / chemistry*
  • Motor Activity / drug effects
  • Oxidative Stress / drug effects
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • RAW 264.7 Cells
  • Rhamnose / analogs & derivatives
  • Rhamnose / therapeutic use
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • 4-((alpha-L-rhamnosyloxy)benzyl)isothiocyanate
  • Anti-Inflammatory Agents
  • Biomarkers
  • Isothiocyanates
  • Lipopolysaccharides
  • moringin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Rhamnose