Soursop

Authored by Dr. Natalie Wood

Soursop is the fruit of the evergreen tree, Annona muricata . This tree is native to tropical regions in the South and Central America. Often used in foods, also widely advertised as an anticancer agent. 

Uses: 
-The flesh of the fruit consists of an edible, white pulp , some fiber, and a core of indigestible, black seeds. Used in foods
-eaten as dessert
-smoothies, fruit juice drinks -candy
-sorbets and ice cream flavoring
-Traditional medicinal uses for diarrhea, liver disease, heart disease, intestinal parasites, diabetes, and cancer. -Pesticides, insecticides and topical insect repellant in latin america
-shampoos for treating lice and ticks 

Toxic component: Annonacin
-Acetogenin -characterized by a long aliphatic chain of 35 to 38 carbons bonded to a γ-lactone α ring, terminally substituted by β-unsaturated methyl, with one or two tetrahydrofurans (THF) located along the hydrocarbon chain.
-It’s structure makes it highly lipophilic and able to cross membranes easily and cross into nerve cells
​-Caparros-Lefebvre and Elbaz (1999) reported in Guadeloupe, atypical parkinsonism was abnormally frequent, and represented 75% of progressive parkinsonism while Parkinson’s disease accounted for only 25% of the cases. 

-This is exceptionally frequent compared to epidemiological data from European countries where atypical parkinsonism accounts for only approximately 5% of all cases
- A higher proportion of patients with atypical parkinsonism (consumed soursop fruit 97%; consumed herbal tea 83%) than patients with Parkinson’s disease (fruit 59%; herbal tea 18%) or control with no Parkinson symptoms (fruit 60%; herbal tea 43%).
-When directly injecting rats for one month with the estimated amounts of annonacin ingested in a year by eating one fruit daily, this induced neurodegeneration in the basal ganglia and mesencephalon (Champy et al., 2004) -As an indication of its potential toxicity, an adult who consumes one fruit or can of nectar a day is estimated to ingest over 1 year the amount of annonacin that induced brain lesions in rats receiving purified annonacin by intravenous infusion.
-Multiple studies showing toxicity in vitro to dopaminergic neurons
-Cultured neurons treated with low doses of annonacin exhibit hallmarks of tauopathy, including increased tau concentration, tau hyperphosphorylation, cell death and somatodendritic redistribution of hyperphosphorylated tau which is that same pathophysiology of progressive supranuclear palsy.
-Studied as a cytotoxic agent for use in cancer chemotherapy
-Extract from the seeds and leaves have IC50 comparable to doxorubicin at .57μg/mL (seed) and .36μg/mL (leaves) compared to .11μg/mL (doxorubicin) in leukemia cells.
-Mechanism of action is via annonacin, the acetogenin causing mitochondrial membrane potential disruption. It inhibits NADH dehydrogenase on Complex I of the electron transport chain. Creates reactive O2 species that can damage DNA and other components of mitochondria
-Annona muricata leaf extract reduced the tumor's size and weight, showed anti-metastatic features, and induced apoptosis in vitro and in vivo of the 4 T1 breast cancer cell lines. Furthermore, it decreased the level of nitric oxide and malondialdehyde in tumor while also increased the level of white blood cell, T-cell, and natural killer cell population. 

​

Pharmacology
-LD 50 >2g/kg
-In IV administration to Rats 3800 and 7600 μg/kg daily caused neurodegeneration over a period of 28 days -it appears that chronic consumption causes the neurodegeneration
​
Presentation
-Levodopa resistant parkinsonism similar to progressive supranuclear palsy
-PSP presents with loss of balance, bradykinesia, rigidity, problems controlling eye movements, issues with speech and swallowing
-Patients in Guadaloupe:
-early postural instability
-supranuclear oculomotor dysfunction
-greater frequency of patients with tremor as compared to typical PSP
-greater frequency of patients with hallucinations as compared to typical PSP

Laboratories
-no laboratory evidence of annonacin toxicity
-annonacin can be identified in brain neurons on autopsy

Treatment/Management
-stop ingestion of soursop
-poor response to levodopa or other parkinson’s treatment agents 

​

Resources
Caparros-Lefebvre, Dominique, Nicolas Sergeant, Andrew Lees, Agnes Camuzat, Susan Daniel, Annie Lannuzel, Alexis Brice, Eduardo Tolosa, Andre Delacourte, and Charles Duyckaerts. "Guadeloupean parkinsonism: a cluster of progressive supranuclear palsy-like tauopathy." Brain 125.4 (2002): 801-11. Web. 9 July 2017.
Champy, Pierre, Alice Melot, Vincent Guérineau Eng, Christophe Gleye, Djibril Fall, Gunter U. Höglinger, Merle Ruberg, Annie Lannuzel, Olivier Laprévote, Alain Laurens, and Reynald Hocquemiller. "Quantification of acetogenins inAnnona muricata linked to atypical parkinsonism in guadeloupe." Movement Disorders 20.12 (2005): 1629-633. Web. 9 July 2017.
Clement, Yuri N., Varune Mahase, Annelise Jagroop, Kelly Kissoon, Aarti Maharaj, Prashant Mathura, Chrys Mc Quan, Divya Ramadhin, and Cherrista Mohammed. "Herbal remedies and functional foods used by cancer patients attending specialty oncology clinics in Trinidad." BMC Complementary and Alternative Medicine 16.1 (2016): n. pag. Web. 09 July 2017.
Coria-Téllez, Ana V., Efigenia Montalvo-Gónzalez, Elhadi M. Yahia, and Eva N. Obledo-Vázquez. "Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity." Arabian Journal of Chemistry (2016): n. pag. Web. 9 July 2017.
Esposti, M. Degli, A. Ghelli, M. Ratta, D. Cortes, and E. Estornell. "Natural substances (acetogenins) from the familyAnnonaceaeare powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I)." Biochemical Journal 301.1 (1994): 161-67. Web. 9 July 2017.
Kuete, Victor, Joachim K. Dzotam, Igor K. Voukeng, Aimé G. Fankam, and Thomas Efferth. "Cytotoxicity of methanol extracts of Annona muricata, Passiflora edulis and nine other Cameroonian medicinal plants towards multi-factorial drug-resistant cancer cell lines." SpringerPlus 5.1 (2016): n. pag. Web.
Salama, Mohamed, and Oscar Arias-Carrión. "Natural toxins implicated in the development of Parkinson’s disease." Therapeutic Advances in Neurological Disorders 4.6 (2011): 361-73. Web. 9 July 2017.
Lannuzel, A., G. U. Hoglinger, S. Verhaeghe, L. Gire, S. Belson, M. Escobar-Khondiker, P. Poullain, W. H. Oertel, E. C. Hirsch, B. Dubois, and M. Ruberg. "Atypical parkinsonism in Guadeloupe: a common risk factor for two closely related phenotypes?" Brain 130.3 (2007): 816-27. Web. 9 July 2017.
Soursop . N.p., n.d. Web. 09 July 2017.