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Tuesday, 19 January 2016

Neurotoxicity of Dietary Supplements from Annonaceae Species

International Journal of Toxicology vol. 34 no. 6 543-550                                     

  1. Matthias Höllerhage1,2,*
  2. Thomas W. Rösler2,*
  3. Magda Berjas2
  4. Rensheng Luo3
  5. Kevin Tran4
  6. Kristy M. Richards4
  7. Armando U. Sabaa-Srur5
  8. José Guilherme S. Maia6
  9. Maria Rosa de Moraes7
  10. Helena T. Godoy7
  11. Günter U. Höglinger1,2
  12. Robert E. Smith4
  1. 1Department of Neurology, Technical University, Munich, Germany
  2. 2German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
  3. 3University of Missouri, St Louis, MO, USA
  4. 4FDA, Lenexa, KS, USA
  5. 5Federal Rural University, Rio de Janeiro, Brazil
  6. 6Universidade Federal do Oeste do Pará, Santarém, PA, Brazil
  7. 7University of Campinas (UNICAMP), São Paulo, Brazil
  8. *Both the authors contributed equally to the article
  1. Robert E. Smith, US FDA, 11510W 80th St, Lenexa, KS 66214, USA. Email: robert.smith@fda.hhs.gov

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.