Preprint / Version 1

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

Authors

  • Shelby Johnson School of Biotechnology and Health Sciences, Wuyi University; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, China; [email protected]
  • Hyun Park Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; [email protected]
  • Nicholas DaSilva Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; [email protected]
  • Dhiraj Vattem Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; [email protected]
  • Hang Ma School of Biotechnology and Health Sciences, Wuyi University; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, China; [email protected]
  • Navindra Seeram Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; [email protected]

Keywords:

Mucuna pruriens, levodopa, Parkinson’s disease, neuroprotection, Caenorhabditis elegans, Drosophila melanogaster

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: Mucuna pruriens, levodopa, Parkinson’s disease, neuroprotection, Caenorhabditis elegans, Drosophila melanogaster

Author Biographies

Shelby Johnson, School of Biotechnology and Health Sciences, Wuyi University; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, China; [email protected]

George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA

Hyun Park, Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; [email protected]

School of Applied Health Sciences and Wellness, Ohio University, Athens, OH 45701, USA

Nicholas DaSilva, Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; [email protected]

George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA

Dhiraj Vattem, Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA; [email protected]

School of Applied Health Sciences and Wellness, Ohio University, Athens, OH 45701, USA

Hang Ma, School of Biotechnology and Health Sciences, Wuyi University; International Healthcare Innovation Institute (Jiangmen), Jiangmen 529020, China; [email protected]

George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA

Navindra Seeram, Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA; [email protected]

George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA

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