番荔枝辛

番荔枝辛
	IUPAC名; (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
別名	番荔枝素
識別
CAS號	111035-65-5
PubChem	354398
ChemSpider	314587
SMILES	CCCCCCCCCCCCC(C1CCC(O1)C(CCCCC(CCCCCC(CC2=CC(OC2=O)C)O)O)O)O;
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;
InChIKey	XNODZYPOIPVPRF-CGWDHHCXBQ
性質
化學式	C35H64O7
摩爾質量	596.88 g·mol−1
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

番荔枝辛（英語：Annonacin）^[1]，別名番荔枝素，是一種有毒物質，屬乙酰原素（英語：Acetogenin）類化合物，其對神經系統有損害作用。其發現於一些番荔枝科植物的果實中，如泡泡果、牛心番荔枝和刺果番荔枝等水果。在西印度群島地區，含有番荔枝辛的果實常被當作傳統藥物使用。

傳統藥物

歷史上西印度群島地區常用番荔枝科植株和果實（特別是刺果番荔枝和釋迦果）以各種形式食用。當地通常將其葉子泡在熱水中飲用，這些含有番荔枝辛的草藥茶在當地民間醫學中被視為一種很好的藥物^[2]。在瓜德羅普島，當地主要因為鎮靜作用而飲用這種茶。而且當地居民從小孩到老人經常食用含有番荔枝辛產品，每天食用也並不罕見^[3]。

在瓜德羅普島，非典型帕金森病在經常飲用含有番荔枝辛的草藥茶的老年男性中很常見。在1996年至1998年間轉入一家診所的87名帕金森病患者中，25％患有帕金森病，36％患有進行性核上性麻痹（英語：progressive supranuclear palsy），39％患有非典型帕金森病^[4]。

神經毒性

番荔枝辛是一種具有致殘性和潛在致死風險的神經毒素^[5]^[6]^[7]。與其他乙酰原素一樣，番荔枝辛是一種線粒體複合體I（英語：mitochondrial complex I）抑制劑（NADH脫氫酶抑制劑）^[6]。NADH脫氫酶負責將NADH轉化為NAD+，以保持線粒體內氫離子濃度梯度，而番荔枝辛會抑制細胞通過氧化磷酸化產生ATP，從而導致細胞凋亡或壞死^[6]。

番荔枝辛對多巴胺能神經元的LD₅₀為 0.018 μM，並對其產生神經退化的損害。其毒性是另一種強NADH脫氫酶抑制劑MPP+的100倍^[6]。相比於MPP+，番荔枝辛毒性作用範圍更廣，除了黑質紋狀體（nigro-striatal system），還對基底核和腦幹核造成嚴重損害^[4]。

由於瓜德羅普島的飲食習慣容易攝入番荔枝辛，導致番荔枝辛與島上進行性核上性麻痹（英語：progressive supranuclear palsy）和非典型帕金森高發病率有關^[4]。一個平均大小的刺果番荔枝果實含有 15 mg番荔枝辛，而一罐市售花蜜含有36 mg番荔枝辛，一杯泡茶則含有 140 μg^[8]。在齧齒動物上的研究結果顯示，連續28天攝入3.8和7.6 mg/kg/日的番荔枝辛會造成和帕金森病一樣的腦損傷^[9]^[10]。據估計，一個成年人每天食用一個水果或一罐花蜜並持續一年，期間攝入的番荔枝辛的量與靜脈注射純番荔枝辛的齧齒動物誘發腦損傷的劑量相同^[8]。

參考文獻

^ 蘇子仁，賴小平 (編). 汉英、英汉中草药化学成分词汇. 北京: 中國中醫藥出版社. 2006.
^ 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
^ 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
^ ^4.0 ^4.1 ^4.2 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
^ Levine, R. A.; Richards, K. M.; Tran, K; Luo, R; Thomas, A. L.; Smith, R. E. Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC-HRMS. Journal of Agricultural and Food Chemistry. 2015, 63 (4): 1053–1056. PMID 25594104. doi:10.1021/jf504500g.
^ ^6.0 ^6.1 ^6.2 ^6.3 Potts, L. F.; Luzzio, F. A.; Smith, S. C.; Hetman, M; Champy, P; Litvan, I. Annonacin in Asimina triloba fruit: Implication for neurotoxicity. NeuroToxicology. 2012, 33 (1): 53–8. PMID 22130466. doi:10.1016/j.neuro.2011.10.009.
^ Le Ven, J.; Schmitz-Afonso, I.; Touboul, D.; Buisson, D.; Akagah, B.; Cresteil, T.; Lewin, G.; Champy, P. Annonaceae fruits and parkinsonism risk: Metabolisation study of annonacin, a model neurotoxin; evaluation of human exposure. Toxicology Letters. 2011, 205: S50–S51. doi:10.1016/j.toxlet.2011.05.197.
^ ^8.0 ^8.1 Champy, P; Melot, A; Guérineau Eng, V; Gleye, C; Fall, D; Höglinger, G. U.; Ruberg, M; Lannuzel, A; Laprévote, O; Laurens, A; Hocquemiller, R. Quantification of acetogenins in Annona muricata linked to atypical Parkinsonism in Guadeloupe. Movement Disorders. 2005, 20 (12): 1629–33. PMID 16078200. S2CID 31508365. doi:10.1002/mds.20632.
^ Lannuzel, A.; Michel, P. P.; Höglinger, G. U.; Champy, P.; Jousset, A.; Medja, F.; Lombès, A.; Darios, F.; et al. The Mitochondrial Complex I Inhibitor Annonacin is Toxic to Mesencephalic Dopaminergic Neurons by Impairment of Energy Metabolism. Neuroscience. 2003, 121 (2): 287–296. PMID 14521988. S2CID 37873631. doi:10.1016/S0306-4522(03)00441-X.
^ Champy, P.; Höglinger, G. U.; Féger, J.; Gleye, C.; Hocquemiller, R.; Laurens, A.; Guérineau, V.; Laprévote, O.; et al. 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. 2003, 88 (1): 63–69. PMID 14675150. S2CID 24056913. doi:10.1046/j.1471-4159.2003.02138.x .

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[1] 蘇子仁，賴小平 (編). 汉英、英汉中草药化学成分词汇. 北京: 中國中醫藥出版社. 2006.

[ross-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

[3] 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

[cap-4] 4.0 ^4.1 ^4.2 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

[5] Levine, R. A.; Richards, K. M.; Tran, K; Luo, R; Thomas, A. L.; Smith, R. E. Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC-HRMS. Journal of Agricultural and Food Chemistry. 2015, 63 (4): 1053–1056. PMID 25594104. doi:10.1021/jf504500g.

[potts-6] 6.0 ^6.1 ^6.2 ^6.3 Potts, L. F.; Luzzio, F. A.; Smith, S. C.; Hetman, M; Champy, P; Litvan, I. Annonacin in Asimina triloba fruit: Implication for neurotoxicity. NeuroToxicology. 2012, 33 (1): 53–8. PMID 22130466. doi:10.1016/j.neuro.2011.10.009.

[7] Le Ven, J.; Schmitz-Afonso, I.; Touboul, D.; Buisson, D.; Akagah, B.; Cresteil, T.; Lewin, G.; Champy, P. Annonaceae fruits and parkinsonism risk: Metabolisation study of annonacin, a model neurotoxin; evaluation of human exposure. Toxicology Letters. 2011, 205: S50–S51. doi:10.1016/j.toxlet.2011.05.197.

[champy-8] 8.0 ^8.1 Champy, P; Melot, A; Guérineau Eng, V; Gleye, C; Fall, D; Höglinger, G. U.; Ruberg, M; Lannuzel, A; Laprévote, O; Laurens, A; Hocquemiller, R. Quantification of acetogenins in Annona muricata linked to atypical Parkinsonism in Guadeloupe. Movement Disorders. 2005, 20 (12): 1629–33. PMID 16078200. S2CID 31508365. doi:10.1002/mds.20632.

[health_parkinsons1-9] Lannuzel, A.; Michel, P. P.; Höglinger, G. U.; Champy, P.; Jousset, A.; Medja, F.; Lombès, A.; Darios, F.; et al. The Mitochondrial Complex I Inhibitor Annonacin is Toxic to Mesencephalic Dopaminergic Neurons by Impairment of Energy Metabolism. Neuroscience. 2003, 121 (2): 287–296. PMID 14521988. S2CID 37873631. doi:10.1016/S0306-4522(03)00441-X.

[10] Champy, P.; Höglinger, G. U.; Féger, J.; Gleye, C.; Hocquemiller, R.; Laurens, A.; Guérineau, V.; Laprévote, O.; et al. 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. 2003, 88 (1): 63–69. PMID 14675150. S2CID 24056913. doi:10.1046/j.1471-4159.2003.02138.x .

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