International Journal of Toxicology November/December 2015 vol. 34 no. 6 543-550
- Matthias Höllerhage1,2,*
- Thomas W. Rösler2,*
- Magda Berjas2
- Rensheng Luo3
- Kevin Tran4
- Kristy M. Richards4
- Armando U. Sabaa-Srur5
- José Guilherme S. Maia6
- Maria Rosa de Moraes7
- Helena T. Godoy7
- Günter U. Höglinger1,2
- Robert E. Smith4⇑
- 1Department of Neurology, Technical University, Munich, Germany
- 2German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
- 3University of Missouri, St Louis, MO, USA
- 4FDA, Lenexa, KS, USA
- 5Federal Rural University, Rio de Janeiro, Brazil
- 6Universidade Federal do Oeste do Pará, Santarém, PA, Brazil
- 7University of Campinas (UNICAMP), São Paulo, Brazil
- *Both the authors contributed equally to the article
- 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.