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

[ Vol. 15 , Issue. 9 ]

Author(s):

Shu-Ying Liu, Shuai Lu, Xiao-Lin Yu, Shi-Gao Yang, Wen Liu, Xiang-Meng Liu, Shao-Wei Wang, Jie Zhu, Mei Ji, Dong-Qun Liu, Zi-Ping Zhang* and Rui-tian Liu*   Pages 856 - 868 ( 13 )

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.

Keywords:

Fruitless wolfberry-sprout extract, Alzheimer's disease, amyloid-β, oligomers, neuroinflammation, oxidative stress.

Affiliation:

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan 750021, State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190



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