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伊利石通过大脑中的Akt/CREB和GSK-3β磷酸化改善阿尔茨海默病Tg-APPswe/PS1dE9小鼠模型的记忆障碍并降低Aβ水平。

Illite improves memory impairment and reduces Aβ level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer׳s disease through Akt/CREB and GSK-3β phosphorylation in the brain.

作者信息

Jeon Songhee, Park Jeong-Eun, Lee Jinhee, Liu Quan Feng, Jeong Ha Jin, Pak Sok Cheon, Yi Sudok, Kim Myung Hun, Kim Chan-Wha, Park Jung-Keug, Kim Geun Woo, Koo Byung-Soo

机构信息

Dongguk University Research Institute of Biotechnology, Seoul 100-715, Republic of Korea.

Dongguk University Research Institute of Biotechnology, Seoul 100-715, Republic of Korea.

出版信息

J Ethnopharmacol. 2015 Feb 3;160:69-77. doi: 10.1016/j.jep.2014.11.029. Epub 2014 Nov 29.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The use of illite in Korean medicine has a long history as a therapeutic agent for various cerebrovascular diseases. According to Dongui Bogam, illite can be used for Qi-tonifying, phlegm dispersing and activation of blood circulation which is an important principle for the treatment of brain-associated diseases.

AIM OF THE STUDY

This study was undertaken to evaluate beneficial effects of illite on the neurodegenerative diseases such as Alzheimer׳s disease (AD).

MATERIAL AND METHODS

The transgenic mice of AD, Tg-APPswe/PS1dE9, were fed with 1% or 3% of illite for 3 months. Behavioral, immunological and ELISA analyses were used to assess memory impairment with additional measurement of Aβ accumulation and plaque deposition in the brain. Other in vitro studies were performed to examine whether illite inhibits the Aβ-induced neurotoxicity in human neuroblastoma cell line, SH-SY5Y cells.

RESULTS

Illite treatment rescued Aβ-induced neurotoxicity on SH-SY5Y cells, which was dependent on the PI3K/Akt activation. Intake of illite improved the Aβ-induced memory impairment and suppressed Aβ levels and plaque deposition in the brain of Tg-APPswe/PS1dE9 mice. Illite increased CREB, Akt, and GSK-3β phosphorylation and suppressed tau phosphorylation in the AD-like brains. Moreover, 1% of illite reduced weight gain and suppressed glucose level in the blood.

CONCLUSION

The present study suggests that illite has the potential to be a useful adjunct as a therapeutic drug for the treatment of AD.

摘要

民族药理学相关性

在韩国医学中,伊利石作为治疗各种脑血管疾病的药物有着悠久的历史。根据《东医宝鉴》记载,伊利石可用于补气、化痰和促进血液循环,这是治疗脑部相关疾病的重要原则。

研究目的

本研究旨在评估伊利石对阿尔茨海默病(AD)等神经退行性疾病的有益作用。

材料与方法

给AD转基因小鼠Tg-APPswe/PS1dE9喂食1%或3%的伊利石,持续3个月。采用行为学、免疫学和酶联免疫吸附测定(ELISA)分析来评估记忆损伤情况,并额外测量大脑中β淀粉样蛋白(Aβ)的积累和斑块沉积。还进行了其他体外研究,以检验伊利石是否能抑制人神经母细胞瘤细胞系SH-SY5Y细胞中Aβ诱导的神经毒性。

结果

伊利石处理可挽救Aβ对SH-SY5Y细胞诱导的神经毒性,这依赖于磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)的激活。摄入伊利石可改善Aβ诱导的记忆损伤,并抑制Tg-APPswe/PS1dE9小鼠大脑中的Aβ水平和斑块沉积。伊利石可增加AD样大脑中cAMP反应元件结合蛋白(CREB)、Akt和糖原合成酶激酶-3β(GSK-3β)的磷酸化,并抑制tau蛋白的磷酸化。此外,1%的伊利石可减少体重增加并抑制血液中的葡萄糖水平。

结论

本研究表明,伊利石有潜力作为治疗AD的辅助治疗药物发挥作用。

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