Zou Juan, Cai Pei-Shan, Xiong Chao-Mei, Ruan Jin-Lan
Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2016 Feb;36(1):21-30. doi: 10.1007/s11596-016-1536-4. Epub 2016 Feb 3.
Alzheimer's disease (AD) is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta (Aβ) peptide in human brains. Oxidative stress and neuroinflammation induced by Aβ in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Aβ25-35 in vivo. Briefly, the AD model was induced by injecting Aβ25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides (200, 400 and 800 mg/kg, p.o.) for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase (SOD), glutathione (GSH), acetylcholine esterase (AChE), and the content of malondialdehyde (MDA) as well as the level of nitric oxide (NO) in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides (400 or 800 mg/kg). All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system.
阿尔茨海默病（AD）是老年人主要的神经退行性疾病之一，其特征是β-淀粉样蛋白（Aβ）肽在人脑中积累和沉积。脑中由Aβ诱导的氧化应激和神经炎症越来越被认为是AD发病机制的原因。本研究旨在确定核桃肽对体内Aβ25-35诱导的神经毒性的保护作用。简要地说，通过向小鼠双侧海马注射Aβ25-35诱导AD模型。动物连续五周用蒸馏水或核桃肽（200、400和800mg/kg，口服）治疗。通过莫里斯水迷宫试验和跳台回避试验研究小鼠的空间学习和记忆能力。为了进一步探讨核桃肽神经保护作用的潜在机制，采用分光光度法测定小鼠海马中超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、乙酰胆碱酯酶（AChE）的活性以及丙二醛（MDA）的含量和一氧化氮（NO）的水平。此外，使用酶联免疫吸附测定法测定样品中8-羟基-2'-脱氧鸟苷（8-OHdG）、肿瘤坏死因子-α（TNF-α）、白细胞介素1β（IL-1β）和IL-6的水平。通过蛋白质印迹分析评估诱导型一氧化氮合酶（iNOS）和核因子κB（NF-κB）在海马中的表达。结果表明，补充核桃肽可有效改善小鼠的认知缺陷和记忆障碍。同时，我们的研究还表明，补充核桃肽（400或800mg/kg）可有效恢复抗氧化酶和炎症介质的水平。上述所有发现表明，核桃肽可能通过减少炎症反应和调节抗氧化系统对AD具有保护作用。
