Annonacin

Annonacin is a potent and lipophilic acetogenin from A. muricata that inhibits mitochondrial complex I (IC₅₀ = 54.8 nM).¹,² Annonacin induces ATP depletion, tau pathologies, and dopaminergic cell death in rats (EC₅₀s = 134, 44.1, and 60.8 nM, respectively). Quantities of annonacin in the fruit and teas made from leaves of A. muricata are such that a cumulative dose sufficient to induce murine neurodegeneration can be attained in humans by regular consumption within one year. This implicates annonacin in the etiology of taupathologies identified in regions of A. muricata consumption. Annonacin also reduces cell survival (ED₅₀ = 0.31 µM in MCF-7 cells) and decreases MCF-7 xenograft tumor size in nude mice at a dose of 50 mg/kg per day.³

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1. Höllerhage, M., Matusch, A., Champy, P., et al. Natural lipophilic inhibitors of mitochondrial complex I are candidate toxins for sporadic neurodegenerative tau pathologies. Exp. Neurol. 220(1), 133-142 (2009).

2. Lannuzel, A., Michel, P.P., Höglinger, G.U., et al. The mitochondrial complex I inhibitor annonacin is toxic to mesencephalic dopaminergic neurons by impairment of energy metabolism. Neuroscience 121(2), 287-296 (2003).

3. Ko, Y.-M., Wu, T.-Y., Wu, Y.-C., et al. Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells. J. Ethnopharmacol. 137(3), 1283-1290 (2001).