Wang Cong, He Ling, Yan Ming, Zheng Guang-yao, Liu Xiao-yang
Department of Pharmacology, China Pharmaceutical University, No. 24 Tong Jia Xiang, Nanjing, 210009,, JiangSu Province, China.
Age (Dordr). 2014;36(4):9676. doi: 10.1007/s11357-014-9676-6. Epub 2014 Jul 1.
Cognitive deficiency and oxidative stress have been well documented in aging and in neurodegenerative disorders such as Alzheimer's disease. In this study, we assessed the therapeutic effect of polyprenols on D-galactose-induced cognitive impairment in mice by testing on of behavioral and cognitive performance. In order to explore the possible role of polyprenols against D-galactose-induced oxidative damages, we assessed various biochemical indicators. Chronic administration of D-galactose (150 mg/kg·d, s.c.) for 7 weeks significantly impaired cognitive performance (both in step-through passive and active avoidance tests) and locomotor activity (in open-field test) and the ability of spatial learning and memory (in Morris water maze test) compared with the control group. The results revealed that polyprenols treatment for 2 weeks significantly ameliorated model mice's cognitive performance and oxidative defense. All groups of polyprenols enhanced the learning and memory ability in step-through passive and active avoidance tests, locomotor activity in open-field test, and the ability of spatial learning and memory in Morris water maze test. Furthermore, high and middle level of polyprenols significantly increased total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px), super oxide dismutase (SOD) activity, neprilysin (NEP), and β-site AβPP cleaving enzyme 1 (BACE1) expression, while nitric oxide (NO), nitric oxide synthase (NOS) activity, malondialdehyde (MDA) concentration, and the level of Aβ1-42 and presenilin 1 (PS1) were decreased. Polyprenols have a significant relieving effect on learning, memory, and spontaneous activities in a D-galactose-induced mouse model and ameliorates cognitive impairment and biochemical dysfunction in mice. In summary, we have demonstrated that polyprenols may ameliorate memory and cognitive impairment via enhancing oxidative defense and affecting generation and dissimilation of Aβ-related enzymes, suggesting that polyprenols represent a novel drug for treating Alzheimer's disease.
认知缺陷和氧化应激在衰老以及神经退行性疾病（如阿尔茨海默病）中已有充分记载。在本研究中，我们通过测试行为和认知表现，评估了聚戊烯醇对D-半乳糖诱导的小鼠认知障碍的治疗效果。为了探究聚戊烯醇对抗D-半乳糖诱导的氧化损伤的可能作用，我们评估了各种生化指标。与对照组相比，连续7周皮下注射D-半乳糖（150 mg/kg·d）显著损害了认知表现（在穿梭箱被动和主动回避试验中）、运动活动（在旷场试验中）以及空间学习和记忆能力（在莫里斯水迷宫试验中）。结果显示，聚戊烯醇治疗2周显著改善了模型小鼠的认知表现和氧化防御能力。所有聚戊烯醇组均增强了穿梭箱被动和主动回避试验中的学习和记忆能力、旷场试验中的运动活动以及莫里斯水迷宫试验中的空间学习和记忆能力。此外，高剂量和中剂量聚戊烯醇显著提高了总抗氧化能力（T-AOC）、谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）活性、中性内肽酶（NEP）以及β-位点淀粉样前体蛋白裂解酶1（BACE1）的表达，同时降低了一氧化氮（NO）、一氧化氮合酶（NOS）活性、丙二醛（MDA）浓度以及Aβ1-42和早老素1（PS1）的水平。聚戊烯醇对D-半乳糖诱导的小鼠模型的学习、记忆和自发活动具有显著的缓解作用，并改善了小鼠的认知障碍和生化功能障碍。总之，我们证明了聚戊烯醇可能通过增强氧化防御以及影响Aβ相关酶的生成和代谢来改善记忆和认知障碍，这表明聚戊烯醇是一种治疗阿尔茨海默病的新型药物。
