Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice
Cognitive-enhancing and antioxidant activities of iridoid glycosides from Scrophularia buergeriana in scopolamine-treated mice
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DOI：
10.1016/j.ejphar.2008.04.015
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发表时间：
2008-06-24
影响因子：
5
通讯作者：
Kim, Young Choong
中科院分区：
文献类型：
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作者：
Jeong, Eun Ju;Lee, Ki Yong;Kim, Young Choong
用Morris水迷宫和被动回避实验评价了玄参中的E-haragoside和8-O-E-p-甲氧基肉桂酰haragide(MCA-Hg)对东莨菪碱所致记忆障碍小鼠的认知增强作用。在Morris水迷宫实验中，E-haragoside和MCA-Hg可明显改善东莨菪碱所致的参考记忆障碍。两种化合物均能改善小鼠的平均逃避潜伏期、平均路径长度和游泳运动。在被动回避实验中，E-haragoside和MCA-Hg(2 mg/kg体重，P.O.)显著改善东莨菪碱诱导的健忘症，其水平高达正常对照组小鼠的70%。多奈哌齐是一种乙酰胆碱酯酶抑制剂，也是治疗AD最广泛使用的药物，作为阳性对照。E-haragoside或MCA-Hg显著抑制大脑皮层和海马区乙酰胆碱酯酶的活性，与多奈哌齐(2 mg/kg体重，P.O.)处理的小鼠的水平相似。此外，东芝总皂甙或MCA-Hg可显著降低东莨菪碱所致记忆障碍小鼠的脑组织总胆红素含量，并可提高谷胱甘肽还原酶、超氧化物歧化酶的活性或含量，降低谷胱甘肽的含量。我们认为这些数据表明E-haragoside或MCA-Hg通过抗乙酰胆碱酯酶和抗氧化机制发挥了强大的认知增强活性。(C)2008爱思唯尔B.V.保留所有权利。
The cognitive-enhancing activities of E-harpagoside and 8-O-E-p-methoxycinnamoylharpagide (MCA-Hg) isolated from Scrophularia buergeriana were evaluated in scopolamine-induced amnesic mice by the Morris water maze and by passive avoidance tests. E-harpagoside and MCA-Hg significantly improved the impairment of reference memory induced by scopolamine in the Morris water maze test. The mean escape latency, the mean path length and swimming movement were also improved by both compounds. In passive avoidance test, E-harpagoside and MCA-Hg (2 mg/kg body weight, p.o.) significantly ameliorated scopolamine-induced amnesia by as much as 70% of the level found in normal control mice. Donepezil, an acetylcholinesterase inhibitor and the most widely used drug for AD treatment was employed as a positive control. The activity of acetylcholinesterase was inhibited significantly by E-harpagoside or MCA-Hg within the cortex and hippocampus to a level similar to that observed in mice treated with donepezil (2 mg/kg body weight, p.o.). Moreover, treatment with E-harpagoside or MCA-Hg to scopolamine-induced amnesic mice significantly decreased TBARS level which was accompanied by an increase in the activities or contents of glutathione reductase, SOD and reduced GSH. We believe these data demonstrate that E-harpagoside or MCA-Hg exerted potent cognitive-enhancing activity through both anti-acetylcholinesterase and antioxidant mechanisms. (C) 2008 Elsevier B.V. All rights reserved.