Yuzu Extract Prevents Cognitive Decline and Impaired Glucose Homeostasis in β-Amyloid-Infused Rats
Yuzu Extract Prevents Cognitive Decline and Impaired Glucose Homeostasis in β-Amyloid-Infused Rats
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DOI：
10.3945/jn.112.173401
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发表时间：
2013-07-01
影响因子：
4.2
通讯作者：
Park, Sunmin
中科院分区：
文献类型：
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作者：
Yang, Hye Jeong;Hwang, Jin Taek;Park, Sunmin
我们的初步研究表明，由β-淀粉样蛋白积聚引起的痴呆损害了外周葡萄糖稳态(未发表)。因此，我们评估了长期口服玉树提取物是否改善了β-淀粉样蛋白诱导的大鼠的认知功能障碍和血糖稳态。雄性大鼠海马CA1区注射β-淀粉样蛋白(25-35)[斑块形成β-淀粉样蛋白；阿尔茨海默病(AD)]或β-淀粉样蛋白(35-25)[无斑块形成β-淀粉样蛋白；C(非阿尔茨海默病对照)]，每天3.6nmol/d，连续14d。AD大鼠分为2组，分别在高脂饲料(43%能量脂肪)中注入3%冷冻干燥的70%玉竹乙醇提取物(AD-Y)或3%糊精(AD-C)。AD-C组表现出更多的海马β-淀粉样蛋白沉积，这在C组中没有被检测到，并且减弱了海马区的胰岛素信号。郁金治疗可防止AD-C大鼠的β-淀粉样蛋白堆积，增加tau的磷酸化，并减弱海马胰岛素信号转导。与β-淀粉样蛋白积聚一致，AD-C大鼠经历了认知功能障碍，而郁金可预防这一障碍。由于饲料消耗的减少，AD-C大鼠的体重增加比C大鼠少，而郁金治疗阻止了饲料消耗的下降。在口服葡萄糖耐量试验中，AD-C组大鼠在糖负荷后40-120min的血糖浓度高于C组，但在0-40min时无明显变化。AD-C组大鼠血清胰岛素浓度显著升高，但不足以将血糖降至正常水平，表明AD-C组大鼠存在胰岛素抵抗和临界性糖尿病状态。虽然AD-C大鼠存在严重的胰岛素抵抗，但AD-Y大鼠表现出正常的糖耐量第一和第二阶段以及胰岛素敏感性和分泌。综上所述，郁祖法可预防β-淀粉样蛋白注射所致的认知功能障碍和能量、血糖稳态受损。
Our preliminary study revealed that dementia induced by beta-amyloid accumulation impairs peripheral glucose homeostasis (unpublished). We therefore evaluated whether long-term oral consumption of yuzu (Citrus junos Tanaka) extract improves cognitive dysfunction and glucose homeostasis in beta-amyloid-induced rats. Male rats received hippocampal CA1 infusions of beta-amyloid (25-35) [plague forming beta-amyloid; Alzheimer disease (AD)] or beta-amyloid (35-25) [non-plaque forming beta-amyloid; C (non-Alzheimer disease control)] at a rate of 3.6 nmol/d for 14 d. AD rats were divided into 2 dietary groups that received either 3% lyophilized 70% ethanol extracts of yuzu (AD-Y) or 3% dextrin (AD-C) in high-fat diets (43% energy as fat). The AD-C group exhibited greater hippocampal beta-amyloid deposition, which was not detected in the C group, and attenuated hippocannpal insulin signaling. Yuzu treatment prevented beta-amyloid accumulation, increased tau phosphorylation, and attenuated hippocampal insulin signaling observed in AD-C rats. Consistent with beta-amyloid accumulation, the AD-C rats experienced cognitive dysfunction, which was prevented by yuzu. AD-C rats gained less weight than did C rats due to decreased feed consumption, and yuzu treatment prevented the decrease in feed consumption. Serum glucose concentrations were higher in AD-C than in C rats at 40-120 min after glucose loading during an oral-glucose-tolerance test, but not at 0-40 min. Serum insulin concentrations were highly elevated in AD-C rats but not enough to lower serum glucose to normal concentrations, indicating that rats in the AD-C group had insulin resistance and a borderline diabetic state. Although AD-C rats were profoundly insulin resistant, AD-Y rats exhibited normal first and second phases of glucose tolerance and insulin sensitivity and secretion. In conclusion, yuzu treatment prevented the cognitive dysfunction and impaired energy and glucose homeostasis induced by beta-amyloid infusion.