Abstract
Alzheimer’s disease (AD) is the world’s most common form of dementia, in which aggregation of amyloid-β (Aβ) is the hallmark. Unfortunately, few medicines have succeeded to completely cure AD. Yangxue Qingnao (YXQN) is a Chinese traditional medicine, and its pharmacological effect is improving cerebral blood flow. In this study, we firstly demonstrated that YXQN reduced AD-like pathology and cognitive impairment in APPswePS1dE9 (APP/PS1) mice with 2 months administration. Our data showed that YXQN substantially ameliorated behavioral defects in 10-month old APP/PS1 mice using Morris Water Maze and Y-maze tests, in which the cognitive ability of YXQN high-dose group approaches to wild type mice. Next, we focused on the brain pathological alterations in the YXQN group by three experiments, including thioflavin-S, congo-red, and Aβ-immunohistochemistry staining. The results demonstrated that the high-dose of YXQN dramatically suppressed amyloid plaques in the hippocampus and cortex of APP/PS1 mice, which showed a 47–72% reduction in plaque deposits, relative to the vehicle group. In addition, our data verified that YXQN decreased the cerebral amyloid load by attenuating β-secretase BACE1 and γ-secretase PS1 in the pathological processing of APP, and promoting the level of α-secretase ADAM10 in the physiological processing of APP to generate more sAPPα, which combats amyloidosis formation, and also carries out neurotropic and neuroprotective effect. Taken together, our results strongly suggest that YXQN could be a potential medicine for AD, and provide new evidence for further AD drug research and development.
Highlights
Alzheimer’s disease (AD) accounts for a large number of dementia cases and afflicts more than 48 million individuals worldwide (Alzheimer’s Association, 2015)
Utilizing 8 month old amyloid precursor protein (APP)/presenilin 1 (PS1) mice and their littermates (WT), we evaluated the possible effects of Yangxue Qingnao (YXQN) on cognitive function of mice after 2 months of drug administration by two kinds of behavioral test, including Morris Water Maze (MWM) tests and Y-maze tests
Our results demonstrated the pronounced effects of YXQN extract, on ameliorating cognitive and memory impairment, and on mitigating the critical pathology in APP/PS1 mice
Summary
Alzheimer’s disease (AD) accounts for a large number of dementia cases and afflicts more than 48 million individuals worldwide (Alzheimer’s Association, 2015). It is a degenerative disease of the central nervous system, with amyloid-β (Aβ) deposition in the brain as a crucial pathological hallmark (Campion et al, 2016), which antedates any other triggered pathological changes of YXQN Attenuates AD Pathophysiological Injuries. As an AD triggering molecule, Aβ is a proteolytic product of the amyloid precursor protein (APP) via the amyloidogenic pathway, in which APP is cleaved by β-secretase (BACE1) to produce extracellular release part-soluble APP peptide-β (sAPPβ), and C-terminal fragment-β (CTFβ)— known as C99. SAPPα provides neuroprotection and promotes neuron outgrowth (Pimplikar and Ghosal, 2011; Milosch et al, 2014)
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