title: Lumbee traditional medicine: Neuroprotective activities of medicinal plants used to treat Parkinson's disease-related symptoms.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD.
  
  
  
  The aims of this study were to (i) document medicinal plants used by Lumbee Indians to treat PD and PD-related symptoms, and (ii) characterize a subset of plant candidates in terms of their ability to alleviate neurotoxicity elicited by PD-related insults and their potential mechanisms of neuroprotection.
  
  
  
  Interviews of Lumbee healers and local people were carried out in Pembroke, North Carolina, and in surrounding towns. Plant samples were collected and prepared as water extracts for subsequent analysis. Extracts were characterized in terms of their ability to induce activation of the nuclear factor E2-related factor 2 (Nrf2) antioxidant response in cortical astrocytes. An extract prepared from Sambucus caerulea flowers (elderflower extract) was further examined for the ability to induce Nrf2-mediated transcription in induced pluripotent stem cell (iPSC)-derived astrocytes and primary midbrain cultures, to ameliorate mitochondrial dysfunction, and to alleviate rotenone- or aSyn-mediated neurotoxicity.
  
  
  
  The ethnopharmacological interviews resulted in the documentation of 32 medicinal plants used to treat PD-related symptoms and 40 plants used to treat other disorders. A polyphenol-rich extract prepared from elderflower activated the Nrf2-mediated antioxidant response in cortical astrocytes, iPSC-derived astrocytes, and primary midbrain cultures, apparently via the inhibition of Nrf2 degradation mediated by the ubiquitin proteasome system. Furthermore, the elderflower extract rescued mitochondrial functional deficits in a neuronal cell line and alleviated neurotoxicity elicited by rotenone and aSyn in primary midbrain cultures.
  
  
  
  These results highlight potential therapeutic benefits of botanical extracts used in traditional Lumbee medicine, and they provide insight into mechanisms by which an elderflower extract could suppress neurotoxicity elicited by environmental and genetic PD-related insults.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA. Electronic address: jacqueta@uw.edu.
authors.forename: Aurélie
authors.initials: A
authors.lastname: de Rus Jacquet
authors.affiliation: Plants for Human Health Institute, Department of Food Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USA. Electronic address: matimmer@ncsu.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Timmers
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA. Electronic address: ma200@purdue.edu.
authors.forename: Sin Ying
authors.initials: SY
authors.lastname: Ma
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA. Electronic address: thiemea@purdue.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thieme
authors.affiliation: Department of Statistics, Purdue University, West Lafayette, IN 47907, USA. Electronic address: mccabe@purdue.edu.
authors.forename: George P
authors.initials: GP
authors.lastname: McCabe
authors.affiliation: University of North Carolina at Pembroke, PO Box 1510, Pembroke, NC 28372, USA. Electronic address: jay.vest@uncp.edu.
authors.forename: Jay Hansford C
authors.initials: JHC
authors.lastname: Vest
authors.affiliation: Plants for Human Health Institute, Department of Food Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USA. Electronic address: mlila@ncsu.edu.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Lila
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA; Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN 47907, USA. Electronic address: jrochet@purdue.edu.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rochet
mesh_terms: D006801:Humans; D007198:Indians, North American; D008519:Medicine, Traditional; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D010946:Plants, Medicinal / Q000737:chemistry*