Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
Life Sci. 2019 Oct 1;234:116739. doi: 10.1016/j.lfs.2019.116739. Epub 2019 Aug 7.
This study aimed to investigate the effect of icariin (referred as ICA) on Alzheimer's disease (AD) model through endoplasmic reticulum (ER) stress pathway.
Nine months male APP/PS1 and wild-type (WT) mice were randomly divided into four groups: APP/PS1 control, APP/PS1 + ICA, WT control and WT + ICA groups. The treated mice were given ICA 60 mg/kg/d and control mice were received the same volume distilled water for consecutive 3 months. The Morris water maze and Novel object recognition were used to detect animals' behavior. Nissl staining was used to observe the neuronal morphology in hippocampus area. Aβ deposition in hippocampal region was observed by immunofluorescence staining. TUNEL staining was used to observe apoptosis. Detection of expression of ER stress related factors by Western blot and real time RT-PCR.
Chronically administrated with ICA compared with APP/PS1 control mice significantly improved the behavior performance, reduced neuronal apoptosis, as well as suppressing the ER stress signaling pathway, including that decreased the level of glucose-regulated protein 78, phosphorylated ER-regulated kinase and phosphorylated eukaryotic initiation factor α, as well activating transcription factor-4, C/EBP homologous protein, DNA damage inducible protein 34 and tribbles homologous protein 3.
Our data indicated that ICA suppressed the ER stress signaling to protect against AD animal model, these findings suggest that a potential point for researching the effect of ICA on neurodegeneration.
本研究旨在通过内质网（ER）应激通路研究淫羊藿苷（ICA）对阿尔茨海默病（AD）模型的影响。
将 9 月龄雄性 APP/PS1 和野生型（WT）小鼠随机分为四组：APP/PS1 对照组、APP/PS1+ICA 组、WT 对照组和 WT+ICA 组。处理组给予 ICA 60mg/kg/d，对照组给予等体积蒸馏水，连续 3 个月。采用 Morris 水迷宫和新物体识别实验检测动物行为。尼氏染色观察海马区神经元形态。免疫荧光染色观察海马区 Aβ 沉积。TUNEL 染色观察细胞凋亡。Western blot 和实时 RT-PCR 检测 ER 应激相关因子的表达。
与 APP/PS1 对照组相比，长期给予 ICA 可显著改善行为表现，减少神经元凋亡，抑制 ER 应激信号通路，包括降低葡萄糖调节蛋白 78、磷酸化 ER 调节激酶和磷酸化真核起始因子α的水平，同时激活转录因子 4、C/EBP 同源蛋白、DNA 损伤诱导蛋白 34 和 Tribbles 同源蛋白 3。
我们的数据表明，ICA 通过抑制 ER 应激信号来保护 AD 动物模型，这些发现提示了研究 ICA 对神经退行性变影响的一个潜在靶点。
