Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease
Protective effects of a dimeric derivative of ferulic acid in animal models of Alzheimer's disease
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DOI：
10.1016/j.ejphar.2016.04.047
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发表时间：
2016-07-05
影响因子：
5
通讯作者：
Song, Dong-Keun
中科院分区：
文献类型：
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作者：
Jung, Jun-Sub;Yan, Ji-Jing;Song, Dong-Keun
阿魏酸是一种具有强效抗氧化和抗炎活性的化合物。我们先前报道了阿魏酸给药对两种阿尔茨海默病（AD）动物模型的保护作用：脑室内（i. c. v.）在小鼠和APP/PS1突变转基因小鼠中注射A β 1-42。在本研究中，使用相同的AD动物模型，我们检查了阿魏酸的二聚衍生物之一KMS 4001的作用。用KMS 4001（30 mg/kg/天）胃内预处理小鼠5天显著减弱A β 1-42（i. c. v.）在被动回避试验和Y-迷宫试验中均引起记忆障碍。APP/PS1突变转基因小鼠在KMS 4001剂量为3和30 mg/kg/天，通过饮用水给药，在KMS 4001治疗开始后1.5和3个月，显示出显著增强的新物体识别记忆。以3和30 mg/kg/天的剂量用KMS 4001处理APP/PS1突变转基因小鼠3个月，显著降低了额叶皮质中的A β 1-40和A β 1-42水平。KMS 4001降低A β和改善新物体识别测试的剂量-反应关系相互对应。综上所述，这些结果表明KMS 4001可能是一种有效的抗AD候选药物。(C)© 2016 Elsevier B. V.版权所有。
Ferulic acid is a compound with potent anti-oxidant and anti-inflammatory activities. We previously reported the protective effects of ferulic acid administration against two animal models of Alzheimer's disease (AD): intracerebroventricular (i.c.v.) injection of A beta 1-42 in mice and APP/PS1 mutant transgenic mice. In this study using the same AD animal models, we examined the effect of KMS4001, one of dimeric derivatives of ferulic acid. Intragastric pretreatment of mice with KMS4001 (30 mg/kg/day) for 5 days significantly attenuated the A beta 1-42 (i.c.v.)-induced memory impairment both in passive avoidance test and in Y-maze test. APP/PS1 mutant transgenic mice at KMS4001 doses of 3 and 30 mg/kg/day via drinking water showed the significantly enhanced novel-object recognition memory at both 1.5 and 3 months after the start of KMS4001 treatment. Treatment of APP/PS1 mutant transgenic mice with KMS4001 for 3 months at the doses of 3 and 30 mg/kg/day markedly decreased A beta 1-40 and A beta 1-42 levels in the frontal cortex. The KMS4001 dose-response relationships for A beta decrease and for improvement in novel-object recognition test corresponded to each other. Taken together, these results suggest that KMS4001 could be an effective drug candidate against AD. (C) 2016 Elsevier B.V. All rights reserved.