无果枸杞芽提取物可挽救阿尔茨海默病转基因小鼠的认知缺陷并减轻其神经病理学损伤。

Fruitless Wolfberry-Sprout Extract Rescued Cognitive Deficits and Attenuated Neuropathology in Alzheimer's Disease Transgenic Mice.

机构信息

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan 750021, China.

出版信息

Curr Alzheimer Res. 2018;15(9):856-868. doi: 10.2174/1567205015666180404160625.

DOI:10.2174/1567205015666180404160625

PMID:29623840

Abstract

BACKGROUND

Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aβ leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reducing Aβ levels and inhibiting Aβ-induced neurotoxicity are feasible therapeutic strategies for AD treatment. Wolfberry has been traditionally used as a natural antioxidant and anti-aging product. However, whether wolfberry species has therapeutic potential on AD remains unknown.

METHOD

The effects of fruitless wolfberry-sprout extract (FWE) on Aβ fibrillation and fibril disaggregation was measured by thioflavin T fluorescence and transmission electron microscope imaging; Aβ oligomer level was determined by dot-blot; Cell viability and apoptosis was assessed by MTT and TUNEL assay. The levels of Aβ40/42, oxidative stress biomarkers and inflammatory cytokines were detected by corresponding kits. 8-month-old male APP/PS1 mice and their age-matched WT littermates were treated with FWE or vehicle by oral administration (gavage) once a day for 4 weeks. Then the cognitive performance was determined using object recognition test and Y-maze test. The Aβ burden and gliosis was evaluated by immunostaining and immunoblotting, respectively.

RESULTS

FWE significantly inhibited Aβ fibrillation and disaggregated the formed Aβ fibrils, lowered Aβ oligomer level and Aβ-induced neuro-cytotoxicity, and attenuated oxidative stress in vitro. Oral administration of FWE remarkably improved cognitive function, reduced Aβ burden, decreased gliosis and inflammatory cytokines release, and ameliorated oxidative stress in the brains of APP/PS1 mice.

CONCLUSION

These findings indicate that FWE is a promising natural agent for AD treatment.

摘要

背景

阿尔茨海默病（AD）是一种以记忆丧失、神经炎症和氧化应激为特征的神经退行性疾病。Aβ的过度产生或清除不足导致其病理性聚集和沉积，这被认为是 AD 的主要神经病理学标志。因此，降低 Aβ水平和抑制 Aβ诱导的神经毒性是 AD 治疗的可行治疗策略。枸杞一直被传统用作天然抗氧化剂和抗衰老产品。然而，枸杞品种对 AD 是否具有治疗潜力尚不清楚。

方法

通过硫黄素 T 荧光和透射电子显微镜成像测量无果枸杞芽提取物（FWE）对 Aβ 纤维形成和纤维解聚的影响；通过斑点印迹法测定 Aβ 寡聚物水平；通过 MTT 和 TUNEL 测定法评估细胞活力和细胞凋亡。通过相应试剂盒检测 Aβ40/42、氧化应激生物标志物和炎症细胞因子的水平。用 FWE 或载体通过口服（灌胃）每天一次处理 8 个月大的雄性 APP/PS1 小鼠及其年龄匹配的 WT 同窝仔鼠 4 周。然后使用物体识别测试和 Y 迷宫测试来确定认知性能。通过免疫染色和免疫印迹分别评估 Aβ 负荷和神经胶质增生。