YXQN Reduces Alzheimer’s Disease-Like Pathology and Cognitive Decline in APPswePS1dE9 Transgenic Mice

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.

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway

“…It is clear from Morris water maze results, that, ART can lessen the escape latency and path length of 3xTg mice, suggesting that ART could recover the learning and spatial memory capacity during AD. The hallmarks of AD are extracellular accumulation of Aβ and intracellular NFT [49,50]. Deposition of Aβ and Tau in brain is the primary characteristic as well as drug target for the diagnostic and therapeutic intervention of AD [51].…”

Longitudinal Assessment of Working Memory Performance in the APPswe/PSEN1dE9 Mouse Model of Alzheimer’s Disease Using an Automated Figure-8-Maze

“…Our results here suggest that in contrast to the reported impairments in long-term spatial and contextual memory, short-term working memory as measured by DAT response accuracy in the F8M is not yet affected in APP/PS1 mice up to 6 moa. Other studies investigating spatial working memory in APP/PS1 mice have shown variable results, with some studies reporting working memory deficits (Kim et al, 2015;Wang et al, 2017) and others not finding a difference between wildtype and transgenic animals (Lalonde et al, 2004;Reiserer et al, 2007;Harrison et al, 2009). Whereas spontaneous alternation is a commonly used measure of working memory, studies on rewarded alternation with variable delay intervals in the APP/PS1 mouse model are sparse.…”

ALWPs Improve Cognitive Function and Regulate Aβ Plaque and Tau Hyperphosphorylation in a Mouse Model of Alzheimer’s Disease

“…For example, Corni fructus has inhibitory activity against BACE1 (β-secretase) and decreases Aβ levels (Youn and Jun, 2012). In another study, Yangxue Qingnao (YXQN), which shares some of the components of ALWPs, significantly decreased cerebral Aβ plaque loads by attenuating the activity of BACE1 (Wang et al, 2017). However, whether the individual components of LWPs or ALWPs are able to affect AD pathology and the associated molecular mechanisms have not been explored in detail.…”