title: Neurotoxicity of Dietary Supplements from Annonaceae Species.
abstract: Dietary supplements containing plant materials of Annonaceae species (Annona muricata L., A. squamosa L., A. mucosa JACQ., A. squamosa × cherimola Mabb.) were extracted by hot, pressurized ethyl acetate and analyzed for their effect in vitro on Lund human mesencephalic neurons. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and cell death was determined by lactate dehydrogenase levels. Three supplements strongly decreased the cell viability at extract concentrations of 1 µg/mL, of which 1 decreased cell viability at 0.1 µg/µL. Also, strong neuronal toxicities of these supplements were found. Cell death was observed at concentrations of 10 µg/mL. The degree of toxicity was comparable to the ones found in Annonaceous fruit extracts. Two fruit pulps of Annonaceae (A. muricata and A. squamosa) showed a reduction in cell viability at lower concentrations. The fruit pulp extract of A. muricata revealed the strongest neurotoxic effect, with 67% cell death at a concentration of 1 µg/mL. A high reduction in cell viability coupled with pronounced cell death was found at 0.1 µg/mL for an Annonaceous seed extract. These results demonstrate that the intake of dietary supplements containing plant material from Annonaceae may be hazardous to health in terms of neurotoxicity.
authors.affiliation: Department of Neurology, Technical University, Munich, Germany German Center for Neurodegenerative Diseases (DZNE), Munich, Germany Both the authors contributed equally to the article.
authors.forename: Matthias
authors.initials: M
authors.lastname: Höllerhage
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Munich, Germany Both the authors contributed equally to the article.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Rösler
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
authors.forename: Magda
authors.initials: M
authors.lastname: Berjas
authors.affiliation: University of Missouri, St Louis, MO, USA.
authors.forename: Rensheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: FDA, Lenexa, KS, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tran
authors.affiliation: FDA, Lenexa, KS, USA.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Richards
authors.affiliation: Federal Rural University, Rio de Janeiro, Brazil.
authors.forename: Armando U
authors.initials: AU
authors.lastname: Sabaa-Srur
authors.affiliation: Universidade Federal do Oeste do Pará, Santarém, PA, Brazil.
authors.forename: José Guilherme S
authors.initials: JG
authors.lastname: Maia
authors.affiliation: University of Campinas (UNICAMP), São Paulo, Brazil.
authors.forename: Maria Rosa de
authors.initials: MR
authors.lastname: Moraes
authors.affiliation: University of Campinas (UNICAMP), São Paulo, Brazil.
authors.forename: Helena T
authors.initials: HT
authors.lastname: Godoy
authors.affiliation: Department of Neurology, Technical University, Munich, Germany German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
authors.affiliation: FDA, Lenexa, KS, USA robert.smith@fda.hhs.gov.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Smith
mesh_terms: D029061:Annonaceae / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019587:Dietary Supplements / Q000633:toxicity*; D005638:Fruit / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D010936:Plant Extracts / Q000633:toxicity; D012639:Seeds / Q000737:chemistry / Q000633:toxicity; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue
keywords: annonaceae; dietary supplements; graviola; neurotoxicity; pawpaw