Neurotoxicity of Dietary Supplements from Annonaceae Species

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.