Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer's disease.
Oleocanthal-rich extra-virgin olive oil enhances donepezil effect by reducing amyloid-β load and related toxicity in a mouse model of Alzheimer's disease.
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DOI：
10.1016/j.jnutbio.2017.12.006
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Kaddoumi A
中科院分区：
文献类型：
--
作者：
Batarseh YS;Kaddoumi A
先前的证据表明，特级初榨橄榄油（EVOO）与减轻淀粉样蛋白-β（Aβ）病理学和改善阿尔茨海默病（AD）小鼠模型的认知功能有关。此外，我们最近报道了EVOO中的酚类化合物oleocanthal对AD病理学的有益作用。目前，可用于靶向AD病理学的药物有限。多奈哌齐是一种乙酰胆碱酯酶抑制剂，批准用于所有AD阶段。据报道，多奈哌齐除了抑制乙酰胆碱酯酶外，还具有有限的Aβ靶向机制。本研究旨在研究食用富含油珊瑚醛的EVOO（以下简称EVOO）作为药用食品对多奈哌齐减轻5xFAD小鼠AD模型Aβ负荷的作用及其相关毒性的增强作用。我们的研究结果表明，EVOO消耗与多奈哌齐联合使用可显著降低Aβ负荷和相关病理变化。Aβ负荷降低至少部分可通过增强Aβ清除途径（包括血脑屏障（BBB）清除和酶降解）以及将淀粉样前体蛋白（APP）加工转向非淀粉样蛋白生成途径来解释。此外，EVOO与多奈哌齐联合上调突触蛋白增强BBB紧密性并减少与Aβ病理学相关的神经炎症。总之，EVOO作为一种医疗食品与多奈哌齐联合使用，通过增强多奈哌齐的非胆碱能机制和提供额外的机制来减轻AD患者中的Aβ相关病理，提供了一种有效的治疗方法。
Previous evidence suggested extra-virgin olive oil (EVOO) is linked to attenuating amyloid-β (Aβ) pathology and improving cognitive function in Alzheimer’s disease (AD) mouse models. In addition, we recently reported the beneficial effect of oleocanthal, a phenolic compound in EVOO, against AD pathology. Currently, medications available to target AD pathology are limited. Donepezil is an acetylcholine esterase inhibitor approved for use for all AD stages. Donepezil has been reported to have limited Aβ-targeting mechanisms beside its acetylcholine esterase inhibition. The aim of this study was to investigate the consumption of EVOO rich with oleocanthal (hereafter EVOO) as a medical food on enhancing the effect of donepezil on attenuating Aβ load and related toxicity in 5xFAD mouse model of AD. Our results showed EVOO consumption in combination with donepezil significantly reduced Aβ load and related pathological changes. Reduced Aβ load could be explained, at least in part, by enhancing Aβ clearance pathways including blood-brain barrier (BBB) clearance and enzymatic degradation, and shifting amyloid precursor protein (APP) processing toward the non-amyloidogenic pathway. Furthermore, EVOO combination with donepezil up-regulated synaptic proteins enhanced BBB tightness and reduced neuro-inflammation associated with Aβ pathology. In conclusion, EVOO consumption as a medical food combined with donepezil offers an effective therapeutic approach by enhancing the non-cholinergic mechanisms of donepezil and by providing additional mechanisms to attenuate Aβ related pathology in AD patients.
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