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

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.