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当归属醇提物 INM-176 改善东莨菪碱或 Aβ(1-42)诱导的小鼠认知功能障碍的记忆作用。

The memory ameliorating effects of INM-176, an ethanolic extract of Angelica gigas, against scopolamine- or Aβ(1-42)-induced cognitive dysfunction in mice.

机构信息

Department of Life and Nanopharmaceutical Science, Seoul, Republic of Korea.

出版信息

J Ethnopharmacol. 2012 Sep 28;143(2):611-20. doi: 10.1016/j.jep.2012.07.019. Epub 2012 Jul 28.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Alzheimer's disease is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death. INM-176 is a standardized ethanolic extract of Angelica gigas Nakai that has been traditionally used in herbal medicine in China, Japan, and Korea to treat anemia or as a sedative. We investigated whether INM-176 exhibits anti-amnesic effects.

MATERIALS AND METHODS

Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist, or amyloid β(1-42) (Aβ(1-42)) protein. Anti-amnesic effects of INM-176 were measured by the passive avoidance and the Morris water maze tasks in mice. We also examined the effect of INM-176 on the acetylcholinesterase activity, as well as Aβ(1-42) protein-induced astrogliosis or cholinergic neuronal loss in the brain.

RESULTS

Scopolamine-induced cognitive dysfunction was significantly attenuated by a single or sub-chronic administration of INM-176 in the passive avoidance and the Morris water maze tasks. A single or sub-chronic administration of INM-176 also ameliorated memory impairments induced by Aβ(1-42) protein. INM-176 inhibited acetylcholinesterase activity in the hippocampal tissue in vitro and ex vivo. In addition, INM-176 attenuated the Aβ(1-42) protein-induced astrocyte activation in the hippocampus as well as cholinergic neuronal damage in the CA3 region of the hippocampus and the nucleus basalis of Meynert.

CONCLUSION

These results suggest that the memory ameliorating effects of INM-176 on scopolamine- or Aβ(1-42) protein-induced memory impairment are mediated, in part, via acetylcholinesterase inhibition and neuroprotective activities.

摘要

民族药理学相关性

阿尔茨海默病是一种与认知障碍和胆碱能神经元死亡相关的神经退行性疾病。INM-176 是当归的一种标准化乙醇提取物,在中国、日本和韩国的传统草药医学中,它被用于治疗贫血或作为镇静剂。我们研究了 INM-176 是否具有抗健忘作用。

材料和方法

通过使用乙酰胆碱能毒蕈碱受体拮抗剂东莨菪碱或淀粉样蛋白β(1-42)(Aβ(1-42))蛋白来诱导记忆障碍。通过被动回避和 Morris 水迷宫任务来测量 INM-176 的抗健忘作用。我们还研究了 INM-176 对乙酰胆碱酯酶活性的影响,以及 INM-176 对大脑中 Aβ(1-42)蛋白诱导的星形胶质细胞增生或胆碱能神经元丢失的影响。

结果

单次或亚慢性给予 INM-176 可显著减轻东莨菪碱诱导的认知功能障碍,以及 Aβ(1-42)蛋白诱导的认知障碍。单次或亚慢性给予 INM-176 还可改善 Aβ(1-42)蛋白诱导的记忆障碍。INM-176 在体外和离体条件下抑制海马组织中的乙酰胆碱酯酶活性。此外,INM-176 可减轻 Aβ(1-42)蛋白诱导的海马星形胶质细胞激活以及海马 CA3 区和 Meynert 基底核的胆碱能神经元损伤。

结论

这些结果表明,INM-176 对东莨菪碱或 Aβ(1-42)蛋白诱导的记忆障碍的改善作用部分是通过乙酰胆碱酯酶抑制和神经保护活性介导的。

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