Abstract
Icaritin (ICT) is the main component in the traditional Chinese herb Epimedium, and it has been shown to have anti-Alzheimer's disease (AD) effects, but its neuroprotective effects and the pharmacological mechanisms are unclear. In the present study, senescence-accelerated mouse prone 8 (SAMP8) mice were randomly divided into a model group and an ICT-treated group. Learning and memory abilities were detected by the Morris water maze assay, and the expression of amyloid beta protein (Aβ) and β-site APP cleavage enzyme 1 (BACE1) was determined by Western blotting and polymerase chain reaction (PCR). Histological changes in CA1 and CA3 were detected by hematoxylin-eosin staining (H&E staining), and the immunohistochemical analysis was used to detect the expression and localization of Bax and Bcl-2. The results showed that compared with the SAMP8 mice, the ICT-treated SAMP8 mice showed improvements in spatial learning and memory retention. In addition, the number of necrotic cells and the morphological changes in CA1 and CA3 areas were significantly alleviated in the group of ICT-treated SAMP8 mice, and the expression of BACE1, Aβ1-42 levels, and the Bax/Bcl-2 ratio in the hippocampus was obviously decreased in the ICT-treated group compared with the control group. The results demonstrated that ICT reduced BACE-1 levels, the contents of Aβ1-42, and the Bax/Bcl-2 ratio, suggesting that ICT might have potential therapeutic benefits by delaying or modifying the progression of AD.
Highlights
Alzheimer’s disease (AD) is the most common neurodegenerative disease and the most common cause of dementia.ere are currently 47 million people worldwide suffering from dementia. is number is expected to increase to 131 million by 2050, increasing the burden on patients and their families and the burden on health and social care systems [1]
We found that ICT can pass through the blood-brain barrier and be detected in the rat brain tissue after intragastric administration. e LC–MS results of ICT are shown in Figure 1. erefore, we aimed to verify whether it has an inhibitory effect on BACE-1 in vivo and the underlying mechanism
senescence-accelerated mouse prone 8 (SAMP8) mice tended to exhibit less time in the target quadrant and more time spent in the other quadrants compared with SAMR1 mice, and ICT increased the time spent by SAMP8 mice in the target quadrant and decreased the time spent in other quadrants (Figure 3(b))
Summary
Alzheimer’s disease (AD) is the most common neurodegenerative disease and the most common cause of dementia.ere are currently 47 million people worldwide suffering from dementia. is number is expected to increase to 131 million by 2050, increasing the burden on patients and their families and the burden on health and social care systems [1]. Ere are currently 47 million people worldwide suffering from dementia. Understanding the cognitive and behavioral manifestations of dementia and their relationships to underlying brain pathology is one of the great challenges that neuropsychologists have faced in the past 50 years [1,2,3]. E drugs currently used in treating AD mainly include acetylcholinesterase inhibitors, N-methyl-D-aspartate receptor antagonists, anti-Aβ drugs, and anti-inflammatory drugs. They have different mechanisms of action, these treatments have not achieved obvious therapeutic effects of AD [4]. The key focus of AD research has been the role of the secretase pathway in amyloid precursor protein (APP) cleavage to form Aβ [5, 6]. BACE1 inhibitors are currently being used in clinical trials to treat AD patients, it remains critical to understand whether BACE1 inhibition significantly affects cognitive function in AD patients [7,8,9]
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