Neurotoxicity of Dietary Supplements from Annonaceae Species

International Journal of Toxicology November/December 2015 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.