Effects of Sesaminol Feeding on Brain Aβ Accumulation in a Senescence-Accelerated Mouse-Prone 8
Effects of Sesaminol Feeding on Brain Aβ Accumulation in a Senescence-Accelerated Mouse-Prone 8
复制标题
DOI：
10.1021/acs.jafc.6b01237
复制
发表时间：
2016-06-22
影响因子：
6.1
通讯作者：
Nakamura, Soichiro
中科院分区：
文献类型：
--
作者：
Katayama, Shigeru;Sugiyama, Haruka;Nakamura, Soichiro
阿尔茨海默病(AD)的特征是细胞外β-淀粉样蛋白(Aβ)聚集体的进行性积聚。最近，加速衰老的小鼠倾向8(SAMP8)模型被认为是一种有用的年龄相关性AD模型。因此，我们使用SAMP8小鼠来研究芝麻木脂素对AD样病理发生的预防作用。在初步的体外研究中，相对于芝麻素、芝麻素和芝麻酚三葡糖苷，芝麻酚对Aβ齐聚和纤维形成的抑制作用最大。因此，芝麻酚被选为进一步的体内评价。在SAMP8小鼠中，灌胃给予芝麻酚(0.05%，w/w，在标准饲料中)超过16周，减少了脑Aβ的积聚，并降低了血清8-羟基脱氧鸟苷，这是氧化应激的指标。此外，芝麻酚增加了ADAM10的基因和蛋白表达，ADAM10是一种主要参与淀粉样前体蛋白的非淀粉样变形成过程的蛋白酶。综上所述，这些数据表明，长期摄入芝麻酚可能会抑制致病性Aβ在大脑中的积累。
Alzheimer's disease (AD) is characterized by the progressive accumulation of extracellular beta-amyloid (A beta) aggregates. Recently, the senescence-accelerated mouse-prone 8 (SAMP8) model was highlighted as a useful model of age-related AD. Therefore, we used the SAMP8 mouse to investigate the preventive effects of sesame lignans on the onset of AD-like pathology. In preliminary in vitro studies, sesaminol showed the greatest inhibitory effect on A beta oligomerization and fibril formation relative to sesamin, sesamolin, and sesaminol triglucoside. Hence, sesaminol was selected for further evaluation in vivo. In SAMP8 mice, feed-through sesaminol (0.05%, w/w, in standard chow) administered over a 16 week period reduced brain A beta accumulation and decreased serum 8-hydroxydeoxyguanosine, an indicator of oxidative stress. Furthermore, sesaminol administration increased the gene and protein expression of ADAM10, which is a protease centrally involved in the non-amyloidogenic processing of amyloid precursor protein. Taken together, these data suggest that long-term consumption of sesaminol may inhibit the accumulation of pathogenic A beta in the brain.