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酸枣仁中的神经保护剂酸枣仁皂苷A可改善由Aβ 1-42诱导的痴呆小鼠模型的行为障碍。

Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Aβ 1-42.

作者信息

Liu Zhi, Zhao Xu, Liu Bing, Liu Ai-jing, Li Huan, Mao Xin, Wu Bo, Bi Kai-shun, Jia Ying

机构信息

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, PR China.

School of Pharmacy, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, PR China.

出版信息

Eur J Pharmacol. 2014 Sep 5;738:206-13. doi: 10.1016/j.ejphar.2014.05.041. Epub 2014 Jun 2.

Abstract

Semen Ziziphi Spinosae (SZS) has been used as a hypnotic-sedative medicine for thousands of years. Recently, SZS has also shown notable neuroprotective activities via anti-oxidative and anti-inflammatory effects in dementia animals. Jujuboside A (JuA), isolated from SZS, has been proved to be a major hypnotic-sedative component of SZS. In the present study, we firstly evaluated the effects of intracerebroventricular (ICV) injection of JuA (0.02 and 0.2mg/kg) for five consecutive days on cognitive impairment induced by ICV injection of Aβ 1-42. The results showed that ICV treatment with JuA significantly mitigated learning and memory impairment in mice induced by Aβ 1-42 as measured by the Y-maze, active avoidance and Morris water maze. Furthermore, ICV treatment with JuA reduced the level of Aβ 1-42 in hippocampus, significantly inhibited the activities of acetylcholinesterase (AChE) and NO, and decreased the amount of the increased malondialdehyde (MDA) in the hippocampus and cerebral cortex of mice treated with ICV injection of Aβ 1-42. Shrinkage of nuclei, swollen and eccentrically dispersed neuronal bodies were observed in hippocampus of AD mice induced by Aβ 1-42, however, JuA noticeably improved the histopathological damage. Cumulatively, the present study indicates that JuA may serve as a potential therapeutic agent for the treatment of Alzheimer' disease.

摘要

酸枣仁作为一种催眠镇静药物已被使用了数千年。最近,酸枣仁在痴呆动物模型中还通过抗氧化和抗炎作用表现出显著的神经保护活性。从酸枣仁中分离出的酸枣仁皂苷A(JuA)已被证明是酸枣仁的主要催眠镇静成分。在本研究中,我们首先评估了连续五天脑室内(ICV)注射JuA(0.02和0.2mg/kg)对ICV注射Aβ 1-42诱导的认知障碍的影响。结果表明,通过Y迷宫、主动回避和莫里斯水迷宫测量,ICV注射JuA显著减轻了Aβ 1-42诱导的小鼠学习和记忆障碍。此外,ICV注射JuA降低了海马中Aβ 1-42的水平,显著抑制了乙酰胆碱酯酶(AChE)和一氧化氮(NO)的活性,并减少了ICV注射Aβ 1-42处理的小鼠海马和大脑皮层中增加的丙二醛(MDA)的量。在Aβ 1-42诱导的AD小鼠海马中观察到细胞核萎缩、神经元体肿胀和偏心分散,然而,JuA显著改善了组织病理学损伤。综上所述,本研究表明JuA可能是治疗阿尔茨海默病的潜在治疗药物。

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