Annonacin

Last updated
Annonacin
Annonacin.svg
Names
Preferred IUPAC name
(5S)-5-Methyl-3-[(2R,8R,13R)-2,8,13-trihydroxy-13-{(2R,5R)-5-[(1R)-1-hydroxytridecyl]oxolan-2-yl}tridecyl]furan-2(5H)-one
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
UNII
  • InChI=1S/C35H64O7/c1-3-4-5-6-7-8-9-10-11-15-21-31(38)33-23-24-34(42-33)32(39)22-17-16-19-29(36)18-13-12-14-20-30(37)26-28-25-27(2)41-35(28)40/h25,27,29-34,36-39H,3-24,26H2,1-2H3/t27-,29+,30+,31+,32+,33+,34+/m0/s1 Yes check.svgY
    Key: XNODZYPOIPVPRF-CGWDHHCXSA-N Yes check.svgY
  • InChI=1/C35H64O7/c1-3-4-5-6-7-8-9-10-11-15-21-31(38)33-23-24-34(42-33)32(39)22-17-16-19-29(36)18-13-12-14-20-30(37)26-28-25-27(2)41-35(28)40/h25,27,29-34,36-39H,3-24,26H2,1-2H3/t27-,29+,30+,31+,32+,33+,34+/m0/s1
    Key: XNODZYPOIPVPRF-CGWDHHCXBQ
  • CCCCCCCCCCCCC(C1CCC(O1)C(CCCCC(CCCCCC(CC2=CC(OC2=O)C)O)O)O)O
  • O=C\1O[C@H](/C=C/1C[C@H](O)CCCCC[C@@H](O)CCCC[C@@H](O)[C@@H]2O[C@@H]([C@H](O)CCCCCCCCCCCC)CC2)C
Properties
C35H64O7
Molar mass 596.890 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Annonacin is a chemical compound with toxic effects, especially in the nervous system, found in some fruits such as the paw paw, custard apples, soursop, and others from the family Annonaceae . It is a member of the class of compounds known as acetogenins. Annonacin-containing fruit products are regularly consumed throughout the West Indies for their traditional medicine uses.

Contents

Traditional medicine

Soursop fruit, a source of annonacin Soursop fruit.jpg
Soursop fruit, a source of annonacin

Historically, plants and fruits of Annonaceae (particularly Annona muricata and Annona squamosa ) have been consumed in various forms throughout the West Indies, usually as hot water extracts of leaves. [1] These annonacin-containing herbal teas are thought to be useful in folk medicine. [1] 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. [2]

It was discovered in Guadeloupe that atypical Parkinsonism was predominant in elderly males, who regularly consume annonacin-containing herbal teas. [3] Of 87 people with Parkinsonism transferred to one clinic between 1996 and 1998, 25% had Parkinson's, while 36% had progressive supranuclear palsy and 39% had atypical Parkinsonism. [3]

Neurotoxicity

Annonacin is a disabling and potentially lethal neurotoxin. [4] [5] [6] Like other acetogenins, it is a mitochondrial complex I (NADH-dehydrogenase) inhibitor. [5] 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. [5]

The LC50 of annonacin is 0.018 μM to dopaminergic neurons, and it is the damage done to these neurons that results in the neurodegenerative effects of the toxin. Annonacin is 100 times more toxic than 1-methyl-4-phenylpyridinium (MPP+), another potent mitochondrial complex I inhibitor. [5] 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. [3]

Annonacin has been linked to the abnormally high incidence of progressive supranuclear palsy as well as atypical Parkinsonism in the Caribbean island of Guadeloupe where consumption of fruits such as the soursop (Annona muricata) is common. [3] An average-sized soursop fruit contains 15 mg of annonacin, while a can of commercial nectar contains 36 mg and a cup of infusion, 140 μg. [7] Studies in rodents indicate that consumption of annonacin (3.8 and 7.6 mg per kg per day for 28 days) caused brain lesions consistent with Parkinson's disease. [8] [9] An adult who consumes a fruit or can of nectar daily over the course of a year is estimated to ingest the same amount of annonacin that induced brain lesions in the rodents receiving purified annonacin intravenously. [7]

Related Research Articles

<i>Asimina</i> North American Genus of fruit trees

Asimina is a genus of small trees or shrubs described as a genus in 1763. Asimina is the only temperate genus in the tropical and subtropical flowering plant family Annonaceae. Asimina have large, simple leaves and large fruit. It is native to eastern North America and collectively referred to as pawpaw. The genus includes the widespread common pawpaw Asimina triloba, which bears the largest edible fruit indigenous to the United States. Pawpaws are native to 26 states of the U.S. and to Ontario in Canada. The common pawpaw is a patch-forming (clonal) understory tree found in well-drained, deep, fertile bottomland and hilly upland habitat. Pawpaws are in the same plant family (Annonaceae) as the custard apple, cherimoya, sweetsop, soursop, and ylang-ylang; the genus is the only member of that family not confined to the tropics.

<span class="mw-page-title-main">Respiratory complex I</span> Protein complex involved in cellular respiration

Respiratory complex I, EC 7.1.1.2 is the first large protein complex of the respiratory chains of many organisms from bacteria to humans. It catalyzes the transfer of electrons from NADH to coenzyme Q10 (CoQ10) and translocates protons across the inner mitochondrial membrane in eukaryotes or the plasma membrane of bacteria.

<span class="mw-page-title-main">Fruit tree</span> Tree which bears fruit

A fruit tree is a tree which bears fruit that is consumed or used by animals and humans — all trees that are flowering plants produce fruit, which are the ripened ovaries of flowers containing one or more seeds. In horticultural usage, the term "fruit tree" is limited to those that provide fruit for human food. Types of fruits are described and defined elsewhere, but would include "fruit" in a culinary sense, as well as some nut-bearing trees, such as walnuts.

<span class="mw-page-title-main">Soursop</span> Species of plant

Soursop is the fruit of Annona muricata, a broadleaf, flowering, evergreen tree. It is native to the tropical regions of the Americas and the Caribbean and is widely propagated. It is in the same genus, Annona, as cherimoya and is in the Annonaceae family.

<span class="mw-page-title-main">Annonaceae</span> Family of flowering plants

The Annonaceae are a family of flowering plants consisting of trees, shrubs, or rarely lianas commonly known as the custard apple family or soursop family. With 108 accepted genera and about 2400 known species, it is the largest family in the Magnoliales. Several genera produce edible fruit, most notably Annona, Anonidium, Asimina, Rollinia, and Uvaria. Its type genus is Annona. The family is concentrated in the tropics, with few species found in temperate regions. About 900 species are Neotropical, 450 are Afrotropical, and the remaining are Indomalayan.

<span class="mw-page-title-main">Cherimoya</span> Edible fruit-bearing species of the genus Annona

The cherimoya, also spelled chirimoya and called chirimuya by the Inca people, is a species of edible fruit-bearing plant in the genus Annona, from the family Annonaceae, which includes the closely related sweetsop and soursop. The plant has long been believed to be native to Ecuador and Peru, with cultivation practised in the Andes and Central America, although a recent hypothesis postulates Central America as the origin instead, because many of the plant's wild relatives occur in this area.

<i>Annona</i> Genus of fruits and plants

Annona or Anona is a genus of flowering plants in the pawpaw/sugar apple family, Annonaceae. It is the second largest genus in the family after Guatteria, containing approximately 166 species of mostly Neotropical and Afrotropical trees and shrubs.

<span class="mw-page-title-main">Custard apple</span> Index of plants with the same common name

Custard apple is a common name for several fruits and may refer to Annonaceae, the custard apple family, which includes the following species referred to as custard apples:

<i>Annona squamosa</i> Species of tree

Annona squamosa is a small, well-branched tree or shrub from the family Annonaceae that bears edible fruits called sugar apples or sweetsops. It tolerates a tropical lowland climate better than its relatives Annona reticulata and Annona cherimola helping make it the most widely cultivated of these species. Annona squamosa is a small, semi-(or late) deciduous, much-branched shrub or small tree 3 to 8 metres tall similar to soursop. It is a native of tropical climate in the Americas and West Indies, and Spanish traders aboard the Manila galleons docking in the Philippines brought it to Asia.

<i>Eurytides marcellus</i> Species of butterfly

Eurytides marcellus, the zebra swallowtail, is a swallowtail butterfly native to the eastern United States and south-eastern Canada. It is the state butterfly of Tennessee. Its distinctive wing shape and long tails make it easy to identify, and its black-and-white-striped pattern is reminiscent of a zebra. The butterflies are closely associated with pawpaws, and are rarely found far from these trees. The green or black caterpillars feed on the leaves of various pawpaw species, while the adults feed on flower nectar and minerals from damp soil.

<i>Annona glabra</i> Tropical fruit tree

Annona glabra is a tropical fruit tree in the family Annonaceae, in the same genus as the soursop and cherimoya. Common names include pond apple, alligator apple, swamp apple, corkwood, bobwood, and monkey apple. The tree is native to Florida in the United States, the Caribbean, Central and South America, and West Africa. It is common in the Everglades. The A. glabra tree is considered an invasive species in Sri Lanka and Australia. It grows in swamps, is tolerant of saltwater, and cannot grow in dry soil.

<i>Asimina triloba</i> Species of tree

Asimina triloba, the American papaw, pawpaw, paw paw, or paw-paw, among many regional names, is a small deciduous tree native to the eastern United States and southern Ontario, Canada, producing a large, yellowish-green to brown fruit. Asimina is the only temperate genus in the tropical and subtropical flowering plant family Annonaceae, and Asimina triloba has the most northern range of all. Well-known tropical fruits of different genera in family Annonaceae include the custard-apple, cherimoya, sweetsop, ylang-ylang, and soursop.

Annonins are a group of chemical compounds classified as acetogenins. They are found in the extracts of Annona seeds. Annonin-based bioinsecticides are used to control Coleoptera (beetle) pests commonly found in stored organic cereal and beans in the country of Brazil. Other different types of annonin-based insecticides, derived from A. mucosa, fight off lepidopteran (moth) pests that infest cabbage leaves, also found in the tropical climates of Brazil. The benefit of using these bioinsecticides is their relatively low cost and no phytotoxicity. These annonin molecules act as overpowering inhibitors of complex I in the electron-transport chain in the mitochondria of quarry pests. In cell membranes of these same pests, annonins also inhibit coenzyme NADH, causing these arthropods to die.

<i>Annona montana</i> Species of tree

Annona montana, the mountain soursop, is a tree and its edible fruit in the Annonaceae family native to Central America, the Amazon, and islands in the Caribbean. It has fibrous fruits. A. montana may be used as a rootstock for cultivated Annonas.

<span class="mw-page-title-main">Acetogenin</span> Group of chemical compounds

Acetogenins are a class of polyketide natural products found in plants of the family Annonaceae. They are characterized by linear 32- or 34-carbon chains containing oxygenated functional groups including hydroxyls, ketones, epoxides, tetrahydrofurans and tetrahydropyrans. They are often terminated with a lactone or butenolide. Over 400 members of this family of compounds have been isolated from 51 different species of plants. Many acetogenins are characterized by neurotoxicity.

<span class="mw-page-title-main">Magnoliids</span> Clade of flowering plants

Magnoliids, Magnoliidae or Magnolianae are a clade of flowering plants. With more than 10,000 species, including magnolias, nutmeg, bay laurel, cinnamon, avocado, black pepper, tulip tree and many others, it is the third-largest group of angiosperms after the eudicots and monocots. The group is characterized by trimerous flowers, pollen with one pore, and usually branching-veined leaves.

<i>Annona crassiflora</i> Species of fruit and plant

Annona crassiflora, commonly known as marolo, araticum cortiça, araticum do cerrado or bruto, is a flowering plant in the Annonaceae family. The flowers of a marolo look like jellyfish wearing hats, and the fruits are sweet and very rough. It is native to Brazil and Paraguay and the fruit is eaten by native peoples in the Brazilian Cerrado. Although it is considered to have potential for cultivation, it has not been domesticated to date.

Pseudohypoxia refers to a condition that mimics hypoxia, by having sufficient oxygen yet impaired mitochondrial respiration due to a deficiency of necessary co-enzymes, such as NAD+ and TPP. The increased cytosolic ratio of free NADH/NAD+ in cells (more NADH than NAD+) can be caused by diabetic hyperglycemia and by excessive alcohol consumption. Low levels of TPP results from thiamine deficiency.

<i>Annona jahnii</i> Species of plant

Annona jahnii is a species of plant in the family Annonaceae. It is native to the Brazil, Colombia and Venezuela. William Edwin Safford, the American botanist who first formally described the species, named it after the Venezuelan scientist, explorer and mountain climber Alfredo Jahn.

References

  1. 1 2 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. Lannuzel, A. and Michel, P. P. (2008). Atypical Parkinsonism in the French West Indies: 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. 1 2 3 4 Caparros-Lefebvre, D., & Elbaz, A. (1999). Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case-control study. The Lancet, 354(9175), 281-286. doi : 10.1016/s0140-6736(98)10166-6
  4. Levine, R. A.; Richards, K. M.; Tran, K; Luo, R; Thomas, A. L.; Smith, R. E. (2015). "Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC-HRMS". Journal of Agricultural and Food Chemistry. 63 (4): 1053–1056. doi:10.1021/jf504500g. PMID   25594104.
  5. 1 2 3 4 Potts, L. F.; Luzzio, F. A.; Smith, S. C.; Hetman, M; Champy, P; Litvan, I (2012). "Annonacin in Asimina triloba fruit: Implication for neurotoxicity". NeuroToxicology. 33 (1): 53–8. doi:10.1016/j.neuro.2011.10.009. PMID   22130466.
  6. Le Ven, J.; Schmitz-Afonso, I.; Touboul, D.; Buisson, D.; Akagah, B.; Cresteil, T.; Lewin, G.; Champy, P. (2011). "Annonaceae fruits and parkinsonism risk: Metabolisation study of annonacin, a model neurotoxin; evaluation of human exposure". Toxicology Letters. 205: S50–S51. doi:10.1016/j.toxlet.2011.05.197.
  7. 1 2 Champy, P; Melot, A; Guérineau Eng, V; Gleye, C; Fall, D; Höglinger, G. U.; Ruberg, M; Lannuzel, A; Laprévote, O; Laurens, A; Hocquemiller, R (2005). "Quantification of acetogenins in Annona muricata linked to atypical Parkinsonism in Guadeloupe". Movement Disorders. 20 (12): 1629–33. doi:10.1002/mds.20632. PMID   16078200. S2CID   31508365.
  8. Lannuzel, A.; Michel, P. P.; Höglinger, G. U.; Champy, P.; Jousset, A.; Medja, F.; Lombès, A.; Darios, F.; et al. (2003). "The Mitochondrial Complex I Inhibitor Annonacin is Toxic to Mesencephalic Dopaminergic Neurons by Impairment of Energy Metabolism". Neuroscience. 121 (2): 287–296. doi:10.1016/S0306-4522(03)00441-X. PMID   14521988. S2CID   37873631.
  9. Champy, P.; Höglinger, G. U.; Féger, J.; Gleye, C.; Hocquemiller, R.; Laurens, A.; Guérineau, V.; Laprévote, O.; et al. (2003). "Annonacin, a Lipophilic Inhibitor of Mitochondrial Complex I, induces Nigral and Striatal Neurodegeneration in Rats: Possible Relevance for Atypical Parkinsonism in Guadeloupe". Journal of Neurochemistry. 88 (1): 63–69. doi: 10.1046/j.1471-4159.2003.02138.x . PMID   14675150. S2CID   24056913.