Anti-amyloidogenic effect of Allium sativum in Alzheimer's transgenic model Tg2576.

Anti-amyloidogenic effect of Allium sativum in Alzheimer's transgenic model Tg2576.
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DOI:
10.1080/j157v03n01_05
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发表时间:
2003-01-01
期刊:
Journal of Herbal Pharmacotherapy
影响因子:
--
通讯作者:
Chauhan, Neelima B.
Chauhan, Neelima B.
中科院分区:
其他
文献类型:
--
作者:
Chauhan, Neelima B.

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高水平的胆固醇与阿尔茨海默病(AD)有关。因此,使用降胆固醇药物如他汀类药物治疗AD引起了相当大的兴趣。然而,他汀类药物刺激炎症反应,可能加重ad病理。虽然大蒜(Allium sativum)历来以其与心血管功能相关的降胆固醇作用而闻名,但没有报道表明其用于治疗AD。目前的研究在过度表达携带瑞典双突变(K670N/M671L) (Tg2576)的人类淀粉样蛋白前体蛋白695的AD转基因小鼠模型中测试了食用大蒜减少淀粉样蛋白负荷的可行性。用陈化大蒜提取物(40 mg/kg/d/4周)处理动物。采用夹心ELISA法检测脑内sAPPalpha、sAbeta40、sAbeta42的水平。结果显示,与野生型和同窝对照相比,未经处理的Tgs中sAPPalpha减少64%,Abeta40和Abeta42升高约21倍。与未处理的Tgs相比,饮食中的大蒜使sAPPalpha增加了25%,使Abeta40和Abeta42分别减少了31%和32%。这些结果表明,一种简单且无创的饮食疗法可以降低阿尔茨海默病可能病例的风险,并减少临床诊断的阿尔茨海默病患者先前存在的淀粉样蛋白负担。
High levels of cholesterol are implicated in potentiating Alzheimer's disease (AD). Therefore, the use of cholesterol-lowering agents such as statins has attracted considerable interest in treating AD. However, statins stimulate inflammatory response, which may aggravate AD-pathology. Although garlic (Allium sativum) is historically known for its hypocholesterolemic effects in relation to cardiovascular functions, no reports indicate its use in treating AD. Current study tested the feasibility of using dietary garlic on the reduction of amyloid burden in a transgenic mouse model of AD that overexpresses the human amyloid precursor protein 695 carrying Swedish double mutation (K670N/M671L) (Tg2576). Animals were treated with aged garlic extract (40 mg/kg/d/4 wks). Cerebral levels of sAPPalpha, sAbeta40, sAbeta42 were analyzed by sandwich ELISA. Results show 64% reduction of sAPPalpha, and apprx21-fold elevation of Abeta40 and Abeta42 in untreated Tgs compared to wild type and littermate controls. Dietary garlic increased sAPPalpha by 25% and de creased Abeta40 and Abeta42 by 31% and 32%, respectively, compared to untreated Tgs. These results suggest a simple and non-invasive dietary therapy for reducing risk of AD in probable cases and reducing preexisting amyloid burden in clinically diagnosed AD cases.