Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer's Disease: In Vitro and in Vivo Studies
Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer's Disease: In Vitro and in Vivo Studies
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DOI：
10.1021/cn400024q
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发表时间：
2013-06-01
影响因子：
5
通讯作者：
Kaddoumi, Amal
中科院分区：
文献类型：
--
作者：
Abuznait, Alaa H.;Qosa, Hisham;Kaddoumi, Amal
油黄酚是特级初榨橄榄油中的一种酚类成分，最近被认为与降低阿尔茨海默病(AD)的风险有关，AD是一种神经退行性疾病，其特征是β-淀粉样蛋白(Aβ)和tau蛋白在大脑中积累。然而，油花酚发挥神经保护作用的机制仍不完全清楚。在此，我们提供了体外和体内证据，证明油黄素可能通过上调血脑屏障(BBB)上的主要Aβ转运蛋白P-糖蛋白(P-gp)和低密度脂蛋白受体相关蛋白-1(LRP1)来增强Aβ从脑中的清除。体外和体内研究结果表明，油花青醛在控制Aβ水平方面具有相似和一致的模式。在培养的小鼠脑内皮细胞中，油黄素处理增加了P-gp和LRP1的表达和活性。I-125-Aβ(40)的脑外流指数(BEI%)研究表明，给C57BL/6野生型小鼠注射特级初榨橄榄油的油黄素可促进脑I-125-Aβ(40)的清除，并使BEI%从对照组的62.0+/-3.0%增加到油黄素处理组的79.9+/-1.6%。脑微血管中P-gp和LRP1表达的增加以及抑制研究证实了这些蛋白的上调在油黄治疗后促进I-125-Aβ(40)清除中的作用。此外，我们的结果显示，油黄处理后，由于Aβ降解酶的上调，I-125-Aβ(40)的降解率显著增加。总之，这些发现提供了实验支持，即特级初榨橄榄油可能通过增强大脑对Aβ的清除来降低AD的潜在风险。
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 beta-amyloid (A beta) 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 A beta clearance from the brain via up-regulation of P-glycoprotein (P-gp) and LDL lipoprotein receptor related protein-1 (LRP1), major A beta 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 A beta levels. In cultured mice brain endothelial cells, oleocanthal treatment increased P-gp and LRP1 expression and activity. Brain efflux index (BEI%) studies of I-125-A beta(40) showed that administration of oleocanthal extracted from extra-virgin olive oil to C57BL/6 wild-type mice enhanced I-125-A beta(40) 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 I-125-A beta(40) clearance after oleocanthal treatment. Furthermore, our results demonstrated significant increase in I-125-A beta(40) degradation as a result of the up-regulation of A beta 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 A beta clearance from the brain.