Levodopa-Reduced Mucuna pruriens Seed Extract Shows Neuroprotective Effects against Parkinson's Disease in Murine Microglia and Human Neuroblastoma Cells, Caenorhabditis elegans, and Drosophila melanogaster

Nutrients. 2018 Aug 22;10(9):1139. doi: 10.3390/nu10091139.

Abstract

Mucuna pruriens (Mucuna) has been prescribed in Ayurveda for various brain ailments including 'kampavata' (tremors) or Parkinson's disease (PD). While Mucuna is a well-known natural source of levodopa (L-dopa), published studies suggest that other bioactive compounds may also be responsible for its anti-PD effects. To investigate this hypothesis, an L-dopa reduced (<0.1%) M. pruriens seeds extract (MPE) was prepared and evaluated for its anti-PD effects in cellular (murine BV-2 microglia and human SH-SY5Y neuroblastoma cells), Caenorhabditis elegans, and Drosophila melanogaster models. In BV-2 cells, MPE (12.5⁻50 μg/mL) reduced hydrogen peroxide-induced cytotoxicity (15.7-18.6%), decreased reactive oxygen species production (29.1-61.6%), and lowered lipopolysaccharide (LPS)-induced nitric oxide species release by 8.9⁻60%. MPE (12.5-50 μg/mL) mitigated SH-SY5Y cell apoptosis by 6.9-40.0% in a non-contact co-culture assay with cell-free supernatants from LPS-treated BV-2 cells. MPE (12.5-50 μg/mL) reduced 6-hydroxydopamine (6-OHDA)-induced cell death of SH-SY5Y cells by 11.85⁻38.5%. Furthermore, MPE (12.5-50 μg/mL) increased median (25%) and maximum survival (47.8%) of C. elegans exposed to the dopaminergic neurotoxin, methyl-4-phenylpyridinium. MPE (40 μg/mL) ameliorated dopaminergic neurotoxin (6-OHDA and rotenone) induced precipitation of innate negative geotaxis behavior of D. melanogaster by 35.3 and 32.8%, respectively. Therefore, MPE contains bioactive compounds, beyond L-dopa, which may impart neuroprotective effects against PD.

Keywords: Caenorhabditis elegans; Drosophila melanogaster; Mucuna pruriens; Parkinson’s disease; levodopa; neuroprotection.

MeSH terms

  • 1-Methyl-4-phenylpyridinium / toxicity
  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Dopamine Agents / toxicity
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / metabolism
  • Humans
  • Levodopa / pharmacology*
  • Male
  • Microglia / drug effects*
  • Microglia / metabolism
  • Mucuna / chemistry*
  • Neuroblastoma / metabolism
  • Neuroprotective Agents / pharmacology*
  • Oxidopamine / toxicity
  • Parkinson Disease / drug therapy
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Seeds / chemistry

Substances

  • Dopamine Agents
  • Neuroprotective Agents
  • Plant Extracts
  • Reactive Oxygen Species
  • Levodopa
  • Oxidopamine
  • 1-Methyl-4-phenylpyridinium