Department of Food Science and Nutrition and Kimchi Research Institute, Pusan National University , Busan 46241, Republic of Korea.
Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration , Gyeongnam 50424, Republic of Korea.
J Agric Food Chem. 2017 Dec 13;65(49):10719-10729. doi: 10.1021/acs.jafc.7b03941. Epub 2017 Nov 28.
Alzheimer's disease (AD) is characterized by progressive cognitive and memory impairment. The major pathological hallmark of AD is the accumulation of amyloid beta (Aβ), which is produced from the amyloid precursor protein (APP) through cleavage of β- and γ-secretase. Recently, dietary plant oil containing ω-3 polyunsaturated fatty acid has become an attractive alternative source to fish oil containing eicosapentaenoic acid or docosahexaenoic acid (DHA). We investigated whether ALA isolated from perilla oil has direct effects on improvement of cognitive ability and molecular mechanisms in APP processing in comparison with DHA. In the present study, ICR mice were treated orally with ALA or DHA (100 mg/kg/day) for 14 days after i.c.v. injection of Aβ. Administration of ALA resulted in a prevention of learning and memory deficit in Aβ-injected mice compared with the control group, as observed in T-maze, novel object recognition, and Morris water maze tests. ALA supplementation also markedly ameliorated the Aβ-induced oxidative stress by inhibition of lipid peroxidation and nitric oxide overproduction in the mouse brain, liver, and kidney, almost down to the levels in DHA-administered group. These effects of ALA on protective mechanisms were related to the regulation of APP processing via promoting nonamyloidogenic pathway such as up-regulation of soluble APP alpha, C-terminal fragment alpha/beta ratio, and A disintegrin and metalloprotease10 protein expressions. Furthermore, ALA inhibited the amyloidogenic pathway through the down-regulation of β-site APP-cleaving enzyme and presenilin2. ALA also enhanced Aβ degradation enzyme, insulin-degrading enzyme. In conclusion, the present study indicated a beneficial effect of ALA in improving the cognitive ability against Aβ, and these effects were comparable to those exerted by DHA. Its neuroprotective effects are mediated, in part, by regulation of APP processing and Aβ degradation, and thus, ALA might be a potential candidate for prevention or treatment of neurodegenerative diseases such as AD.
阿尔茨海默病（AD）的特征是进行性认知和记忆障碍。AD 的主要病理标志是淀粉样β（Aβ）的积累，Aβ是由淀粉样前体蛋白（APP）通过β-和γ-分泌酶的切割产生的。最近，含有ω-3 多不饱和脂肪酸的植物性食用油已成为一种有吸引力的替代来源，可替代含有二十碳五烯酸或二十二碳六烯酸（DHA）的鱼油。我们研究了与 DHA 相比，来自紫苏油的 ALA 是否对改善认知能力和 APP 加工的分子机制有直接作用。在本研究中，我们用 Aβ 脑室内注射后连续 14 天，通过口服给 ICR 小鼠喂食 ALA 或 DHA（100mg/kg/天）。与对照组相比，ALA 的给药可预防 Aβ 注射小鼠的学习和记忆缺陷，如 T 迷宫、新物体识别和 Morris 水迷宫测试所示。ALA 补充还通过抑制脂质过氧化和一氧化氮的过度产生，显著改善了 Aβ 诱导的氧化应激，在小鼠脑、肝和肾中的水平几乎降低到 DHA 给药组。ALA 对保护机制的这些影响与通过上调可溶性 APPα、C 端片段α/β 比和 A 分解素和金属蛋白酶 10 蛋白表达来促进非淀粉样形成途径有关。此外，ALA 通过下调β-位点 APP 切割酶和早老素 2 来抑制淀粉样形成途径。ALA 还增强了 Aβ 降解酶胰岛素降解酶。总之，本研究表明 ALA 对改善认知能力有有益作用，可改善对 Aβ 的作用，其效果与 DHA 相当。其神经保护作用部分是通过调节 APP 加工和 Aβ 降解来介导的，因此，ALA 可能是预防或治疗阿尔茨海默病等神经退行性疾病的潜在候选药物。
