Annonacin

Traditional medicine

Historically, plants and fruits of Annonaceae (particularly Annona muricata and Annona squamosa) have been consumed in various forms throughout the Caribbean, usually as hot water extracts of leaves. These annonacin-containing herbal teas are thought to be useful in folk medicine.

It was discovered in Guadeloupe that atypical Parkinsonism was predominant in elderly males, who regularly consume annonacin-containing herbal teas.

Neurotoxicity

Annonacin is a disabling and potentially lethal neurotoxin. Like other acetogenins, it is a mitochondrial complex I (NADH-dehydrogenase) inhibitor, as determined in vitro. As NADH-dehydrogenase is responsible for the conversion of NADH to NAD+ as well as the establishment of a proton gradient in the mitochondria, annonacin disables the ability of a cell to generate ATP through oxidative phosphorylation, leading to cell apoptosis or necrosis.

In vitro, the LC50 of annonacin is 0.018 μM to dopaminergic neurons, and by experimental interpretation, damage to these neurons appears to cause the neurodegenerative effects of the toxin. Annonacin is 100 times more toxic than 1-methyl-4-phenylpyridinium (MPP+), another potent mitochondrial complex I inhibitor. Compared to MPP+, annonacin produces a wider and more dramatic loss of neurons, not only in the nigro-striatal system, but in the basal ganglia and brainstem nuclei as well.

Annonacin has been linked to the abnormally high incidence of progressive supranuclear palsy and atypical Parkinsonism in the Caribbean island of Guadeloupe where consumption of fruits, such as the soursop (Annona muricata), is common.

References

References

1. Ross, I. A. (2003). Annona muricata L. Medicinal Plants of the World, Vol. 1: Chemical Constituents, Traditional and Modern Medicinal Uses,1, 133-142. {{doi. 10.1385/1-59259-365-8:133
2. On the Caribbean island of [[Guadeloupe]], such teas are consumed mainly for their sedative qualities. Use of annonacin products in Guadeloupe often lasts from early childhood through old age, and daily consumption is not uncommon.Lannuzel, A. and Michel, P. P. (2008). Atypical Parkinsonism in the French-colonized Caribbean countries: The Plant Toxin Annonacin as a Potential Etiological Factor. Cortico-Subcortical Dynamics in Parkinson¿s Disease, 1-8. {{doi. 10.1007/978-1-60327-252-0_18
3. 10.1016/s0140-6736(98)10166-6
4. (2015). "Determination of Neurotoxic Acetogenins in Pawpaw (''Asimina triloba'') Fruit by LC-HRMS". Journal of Agricultural and Food Chemistry.
5. (2011). "Annonaceae fruits and parkinsonism risk: Metabolisation study of annonacin, a model neurotoxin; evaluation of human exposure". Toxicology Letters.
6. (2012). "Annonacin in Asimina triloba fruit: Implication for neurotoxicity". NeuroToxicology.