Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both Aβ and Tau pathologies
文献类型：期刊论文
| 作者 | Li Cong3; Guo Xiaodan2; Lei Min2 ; Wu Jiayi2; Jin Jiazhen2; Shi Xiaofan2; Zhu Zhiyuan2; Rukachaisirikul Vatcharin1; Hu Lihong2; Wen Tieqiao3
|
| 刊名 | Acta Pharmacologica Sinica
 |
| 出版日期 | 2017 |
| 卷号 | 38期号:1页码:9 |
| 关键词 | Alzheimer's disease Thamnolia vermicularis SH-SY5Y cells APP/PS1 transgenic mice senile plaque cognition amyloid-β Tau autophagy BACE1 GSK3β PI_3K |
| ISSN号 | 1671-4083 |
| 英文摘要 | Considering the complicated pathogenesis of Alzheimer's disease (AD), multi-targets have become a focus in the discovery of drugs for treatment of this disease. In the current work, we established a multi-target strategy for discovering active reagents capable of suppressing both Aβ level and Tau hyperphosphorylation from natural products, and found that the ethanol extract of Thamnolia vermicularis (THA) was able to improve learning ability in APP/PS1 transgenic mice by inhibiting both Aβ levels and Tau hyperphosphorylation. SH-SY5Y and CHO-APP/BACE1 cells and primary astrocytes were used in cell-based assays. APP/PS1 transgenic mice B6C3-Tg(APP_(swe), PSldE9) were administered THA (300 mg·kg~(-1)·d~(-1), ig) for 100 d. After the administration was completed, the learning ability of the mice was detected using a Morris water maze (MWM) assay; immunofluorescence staining, Congo red staining and Thioflavine S staining were used to detect the senile plaques in the brains of the mice. ELISA was used to evaluate Aβ and sAPPβ contents, and Western blotting and RT-PCR were used to investigate the relevant signaling pathway regulation in response to THA treatment. In SH-SY5Y cells, THA (1,10, 20 μg/mL) significantly stimulated PI_3K/AKT/mTOR and AMPK/raptor/mTOR signaling-mediated autophagy in the promotion of Aβ clearance as both a PI_3K inhibitor and an AMPK indirect activator, and restrained Aβ production as a suppressor against PERK/elF2α-mediated BACE1 expression. Additionally, THA functioned as a GSK3β inhibitor with an IC_(50) of 1.32±0.85 μg/mL, repressing Tau hyperphosphorylation. Similar effects on Aβ accumulation and Tau hyperphosphorylation were observed in APP/PS1 transgenic mice treated with THA. Furthermore, administration of THA effectively improved the learning ability of APP/PS1 transgenic mice, and markedly reduced the number of senile plaques in their hippocampus and cortex. The results highlight the potential of the natural product THA for the treatment of AD. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/292982]  |
| 专题 | 中国科学院上海药物研究所 |
| 作者单位 | 1.宋卡王子大学 2.中国科学院上海药物研究所 3.上海大学 |
| 推荐引用方式 GB/T 7714 | Li Cong,Guo Xiaodan,Lei Min,et al. Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both Aβ and Tau pathologies[J]. Acta Pharmacologica Sinica,2017,38(1):9. |
| APA | Li Cong.,Guo Xiaodan.,Lei Min.,Wu Jiayi.,Jin Jiazhen.,...&Shen Xu.(2017).Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both Aβ and Tau pathologies.Acta Pharmacologica Sinica,38(1),9. |
| MLA | Li Cong,et al."Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both Aβ and Tau pathologies".Acta Pharmacologica Sinica 38.1(2017):9. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。