Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model.
Oleocanthal enhances amyloid-β clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model.
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DOI：
10.1021/acschemneuro.5b00190
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发表时间：
2015-11-18
影响因子：
5
通讯作者：
Kaddoumi A
中科院分区：
文献类型：
--
作者：
Qosa H;Batarseh YS;Mohyeldin MM;El Sayed KA;Keller JN;Kaddoumi A
许多临床和临床前研究表明，特级初榨橄榄油（EVOO）的饮食消费具有多种健康促进作用，可以保护和降低患阿尔茨海默病（AD）的风险。此外，最近的研究将这种保护作用与EVOO的酚类开环环烯醚萜成分oleocanthal联系起来。油珊瑚醛对AD的这种保护作用与其在体外防止淀粉样蛋白-β（Aβ）和tau聚集，并在体内增强野生型小鼠脑中Aβ清除的能力有关;然而，其在AD小鼠模型中的作用尚不清楚。在目前的研究中，我们研究了在TgSwDI（AD的动物模型）中油珊瑚醛对AD病理标志的影响。用oleocanthal处理小鼠4周显著降低海马实质和微血管中的淀粉样蛋白负荷。这种降低与Aβ穿过血脑屏障（BBB）的脑清除率增强相关。进一步的机制研究表明，oleocanthal增加BBB中重要的淀粉样蛋白清除蛋白（包括P-糖蛋白和LRP 1）的表达，并激活小鼠脑中ApoE依赖性淀粉样蛋白清除途径。在这些小鼠的脑中，油珊瑚醛的抗炎作用也是明显的，其中它能够降低星形胶质细胞活化和IL-1β水平。最后，我们可以概括在体外基于人类的模型中观察到的油刺醛的保护作用，这可以反驳对油刺醛的反应的物种差异。总之，体内和体外研究的结果进一步支持了油珊瑚醛对AD进展的保护作用。
Numerous clinical and preclinical studies have suggested several health promoting effects for the dietary consumption of extra-virgin olive oil (EVOO) that could protect and decrease the risk of developing Alzheimer’s disease (AD). Moreover, recent studies have linked this protective effect to oleocanthal, a phenolic secoiridoid component of EVOO. This protective effect of oleocanthal against AD has been related to its ability to prevent amyloid-β (Aβ) and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild type mice in vivo; however, its effect in a mouse model of AD is not known. In the current study, we investigated the effect of oleocanthal on pathological hallmarks of AD in TgSwDI, an animal model of AD. Mice treatment for 4 weeks with oleocanthal significantly decreased amyloid load in the hippocampal parenchyma and microvessels. This reduction was associated with enhanced cerebral clearance of Aβ across the blood-brain barrier (BBB). Further mechanistic studies demonstrated oleocanthal to increase the expression of important amyloid clearance proteins at the BBB including P-glycoprotein and LRP1, and to activate the ApoE-dependent amyloid clearance pathway in the mice brains. The anti-inflammatory effect of oleocanthal in the brains of these mice was also obvious where it was able to reduce astrocytes activation and IL-1β levels. Finally, we could recapitulate the observed protective effect of oleocanthal in an in vitro human-based model, which could argue against species difference in response to oleocanthal. In conclusion, findings from in vivo and in vitro studies provide further support for the protective effect of oleocanthal against the progression of AD.