Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both A beta and Tau pathologies

doi:10.1038/aps.2016.94

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第三研究室

	Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both A beta and Tau pathologies
	Li, Cong 1,3; Gu, Xiao-dan 3; Lei, Min3 ; Wu, Jia-yi 3; Jin, Jia-zhen 3; Shi, Xiao-fan 3; Zhu, Zhi-yuan 3; Rukachaisirikul, Vatcharin 2; Hu, Li-hong 3; Wen, Tie-qiao 1
刊名	ACTA PHARMACOLOGICA SINICA
	2017-01
卷号	38 期号:1 页码:9-28
关键词	Alzheimer's disease Thamnolia vermicularis SH-SY5Y cells APP/PS1 transgenic mice senile plaque cognition amyloid-beta Tau autophagy BACE1 GSK3 beta PI3K
ISSN号	1671-4083
DOI	10.1038/aps.2016.94
文献子类	Article
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 A beta 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 A beta 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), PS1dE9)] 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 All and sAPP beta 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 mu g/mL) significantly stimulated PI3K/AKT/mTOR and AMPK/raptor/mTOR signaling mediated autophagy in the promotion of A beta clearance as both a PI3K inhibitor and an AMPK indirect activator, and restrained All production as a suppressor against PERK/eIF2 alpha-mediated BACE1 expression. Additionally, THA functioned as a GSK3 beta inhibitor with an IC50 of 1.32 +/- 0.85 mu g/mL, repressing Tau hyperphosphorylation. Similar effects on A beta 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.
资助项目	National Natural Science Foundation of China[81220108025] ; National Natural Science Foundation of China[81473141] ; National Natural Science Foundation of China[81273556] ; NSFC-TRF collaboration projects[81561148011] ; NSFC-TRF collaboration projects[DBG5980001] ; Drug Innovation Project of SIMM[CASIMM0120154035]
WOS关键词	TREATING ALZHEIMERS-DISEASE ; SH-SY5Y NEUROBLASTOMA-CELLS ; AMYLOID PRECURSOR PROTEIN ; MEMORY IMPAIRMENT ; BACE1 EXPRESSION ; AUTOPHAGY ; PHOSPHORYLATION ; PATHWAY ; DEGRADATION ; INHIBITOR
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000393540900002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275739]
专题	药理学第三研究室上海中药现代化研究中心
通讯作者	Hu, Li-hong; Shen, Xu
作者单位	1.Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China; 2.Prince Songkla Univ, Dept Chem, Fac Sci, Hat Yai 90112, Songkhla, Thailand 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Li, Cong,Gu, Xiao-dan,Lei, Min,et al. Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both A beta and Tau pathologies[J]. ACTA PHARMACOLOGICA SINICA,2017,38(1):9-28.
APA	Li, Cong.,Gu, Xiao-dan.,Lei, Min.,Wu, Jia-yi.,Jin, Jia-zhen.,...&Shen, Xu.(2017).Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both A beta and Tau pathologies.ACTA PHARMACOLOGICA SINICA,38(1),9-28.
MLA	Li, Cong,et al."Thamnolia vermicularis extract improves learning ability in APP/PS1 transgenic mice by ameliorating both A beta and Tau pathologies".ACTA PHARMACOLOGICA SINICA 38.1(2017):9-28.