ACS Chem Neurosci：揭示橄榄油预防阿尔茨海默病机制

食用特级初榨橄榄油(extra virgin olive oil)如何精确地有助于降低患上阿尔茨海默病(Alzheimer's disease， AD)的风险是一个谜。在一项新的研究中，研究人员报道解决这个谜的关键可能在于橄榄油中的一种组分，这个组分有助于将异常的AD蛋白从大脑中运输出去。相关研究结果于2013年2月15日在线发表在ACS Chemical Neuroscience期刊上，论文标题为“Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease： In Vitro and in Vivo Studies”。

Amal Kaddoumi和同事们注意到在全世界，AD影响着大约数千万人，但是它的发病率在地中海国家中比较低。科学家们曾经将它归结于橄榄油中高含量的有益于健康的单不饱和脂肪，因而这些单不饱和脂肪在地中海饮食中被大量食用。新近的研究提示着这种实际的保护性试剂可能是一种被称作刺激醛(Oleocanthal)的物质。这种物质阻止神经细胞在AD中遭受损伤。

在最新的这项研究中，Kaddoumi和同事们寻求证据来证实橄榄油刺激醛是否有助于降低大脑中的β-淀粉样蛋白(beta-amyloid， Aβ)堆积，其中这种堆积被认为是AD的罪魁祸首。

作为对人研究的替代，他们追踪了橄榄油刺激醛在实验室小鼠大脑和体外培养的小鼠大脑细胞中的影响。在这种实验中，橄榄油刺激醛持续地促进两种蛋白和关键性酶的产生，其中这些蛋白和酶被认为在移除大脑内Aβ中发挥着关键性作用。论文结论为“在地中海饮食中，源自特级初榨橄榄油的刺激醛潜在地降低患上AD或相关的神经元退行性痴呆症的风险。”

DOI: 10.1021/cn400024q

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Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer’s Disease: In Vitro and in Vivo Studies

Alaa H-Abuznait , Hisham Qosa , Belnaser A-Busnena , Khalid A-El Sayed and Amal Kaddoumi.

Oleocanthal, a phenolic component of extra-virgin olive oil, has been recently linked to reduced risk of Alzheimer’s disease (AD), a neurodegenerative disease that is characterized by accumulation of β-amyloid (Aβ) and tau proteins in the brain. However, the mechanism by which oleocanthal exerts its neuroprotective effect is still incompletely understood. Here, we provide in vitro and in vivo evidence for the potential of oleocanthal to enhance Aβ clearance from the brain via up-regulation of P-glycoprotein (P-gp) and LDL lipoprotein receptor related protein-1 (LRP1), major Aβ transport proteins, at the blood-brain barrier (BBB). Results from in vitro and in vivo studies demonstrated similar and consistent pattern of oleocanthal in controlling Aβ levels. In cultured mice brain endothelial cells, oleocanthal treatment increased P-gp and LRP1 expression and activity. Brain efflux index (BEI%) studies of 125I-Aβ40 showed that administration of oleocanthal extracted from extra-virgin olive oil to C57BL/6 wild-type mice enhanced 125I-Aβ40 clearance from the brain and increased the BEI% from 62.0 ± 3.0% for control mice to 79.9 ± 1.6% for oleocanthal treated mice. Increased P-gp and LRP1 expression in the brain microvessels and inhibition studies confirmed the role of up-regulation of these proteins in enhancing 125I-Aβ40 clearance after oleocanthal treatment. Furthermore, our results demonstrated significant increase in 125I-Aβ40 degradation as a result of the up-regulation of Aβ degrading enzymes following oleocanthal treatment. In conclusion, these findings provide experimental support that potential reduced risk of AD associated with extra-virgin olive oil could be mediated by enhancement of Aβ clearance from the brain.