TY - JOUR
T1 - Annonacin in Asimina triloba fruit
T2 - Implication for neurotoxicity
AU - Potts, Lisa F.
AU - Luzzio, Frederick A.
AU - Smith, Scott C.
AU - Hetman, Michal
AU - Champy, Pierre
AU - Litvan, Irene
N1 - Funding Information:
The assistance of Ms. Juan Chen and Dr. Neal Stolowich in recording 1 H and 13 C NMR spectra and of research students Mr. Scott Jones and Ms. Sarah Fox are gratefully acknowledged as well as the advice of Drs. Martha Bickford, Theo Hagg, and David Hein. Support of the Mass Spectrometry Facility and specifically the assistance of Dr. Bogdan Bogdanov of the University of Louisville CREAM Center supported by NSF/EPSCOR grant EPS-0447479 is also gratefully acknowledged. Support from the CEGIB through the NIEHS grant P30ES014443 is also gratefully acknowledged. Dr. Litvan is supported by NIH grant R01 PAS-03–092 , National Parkinson Foundation and Parkinson Support Center of Kentuckiana, and is the founder and CEO of the Litvan Neurological Research Foundation. The generosity of Dr. Samuel Weakly and Ms. Lydia B. Miller for donating research funds for this project is gratefully acknowledged.
PY - 2012/1
Y1 - 2012/1
N2 - Introduction: The acetogenin, annonacin, from the tropical annonaceous plant Annona muricata, is a lipophilic, mitochondrial complex I inhibitor reported to be more toxic than rotenone to mesencephalic neurons. The temperate annonaceous plant Asimina triloba (pawpaw) is native to the Eastern United States and products are available online. This study determined whether annonacin is in the pawpaw fruit pulp and whether it or the crude ethyl acetate extract is toxic to cortical neurons. Methods: Pawpaw extract was prepared by pulp extraction with methanol and liquid-liquid partitioning with ethyl acetate (EtOAc). Annonacin was isolated from the crude EtOAc extract via column chromatography using a gradient solvent system of increasing polarity. Mass spectroscopy, nuclear magnetic resonance and infrared spectroscopy were used to compare isolated material with synthetic annonacin data and a natural annonacin sample. Toxicity of isolated annonacin and the total EtOAc extract was determined in primary rat cortical neurons using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results: The average concentration of annonacin in the fruit pulp was 0.0701 ± 0.0305 mg/g. Purified annonacin (30.07 μg/ml) and crude EtOAc extract (47.96 μg/ml) induced 50% death of cortical neurons 48 h post treatment. Annonacin toxicity was enhanced in the presence of crude extract. Discussion: Pawpaw fruit contains a high concentration of annonacin, which is toxic to cortical neurons. Crude fruit extract also induced neurotoxicity, highlighting the need for additional studies to determine the potential risks of neurodegeneration associated with chronic exposure to pawpaw products.
AB - Introduction: The acetogenin, annonacin, from the tropical annonaceous plant Annona muricata, is a lipophilic, mitochondrial complex I inhibitor reported to be more toxic than rotenone to mesencephalic neurons. The temperate annonaceous plant Asimina triloba (pawpaw) is native to the Eastern United States and products are available online. This study determined whether annonacin is in the pawpaw fruit pulp and whether it or the crude ethyl acetate extract is toxic to cortical neurons. Methods: Pawpaw extract was prepared by pulp extraction with methanol and liquid-liquid partitioning with ethyl acetate (EtOAc). Annonacin was isolated from the crude EtOAc extract via column chromatography using a gradient solvent system of increasing polarity. Mass spectroscopy, nuclear magnetic resonance and infrared spectroscopy were used to compare isolated material with synthetic annonacin data and a natural annonacin sample. Toxicity of isolated annonacin and the total EtOAc extract was determined in primary rat cortical neurons using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results: The average concentration of annonacin in the fruit pulp was 0.0701 ± 0.0305 mg/g. Purified annonacin (30.07 μg/ml) and crude EtOAc extract (47.96 μg/ml) induced 50% death of cortical neurons 48 h post treatment. Annonacin toxicity was enhanced in the presence of crude extract. Discussion: Pawpaw fruit contains a high concentration of annonacin, which is toxic to cortical neurons. Crude fruit extract also induced neurotoxicity, highlighting the need for additional studies to determine the potential risks of neurodegeneration associated with chronic exposure to pawpaw products.
KW - Annonaceous acetogenins
KW - Annonacin
KW - Asimina triloba
KW - Neurotoxicity
KW - Pawpaw
UR - http://www.scopus.com/inward/record.url?scp=83155191150&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=83155191150&partnerID=8YFLogxK
U2 - 10.1016/j.neuro.2011.10.009
DO - 10.1016/j.neuro.2011.10.009
M3 - Article
C2 - 22130466
AN - SCOPUS:83155191150
VL - 33
SP - 53
EP - 58
JO - NeuroToxicology
JF - NeuroToxicology
SN - 0161-813X
IS - 1
ER -