Abstract
Ginseng has been shown to produce a cognitive improvement effect. The key molecular components in ginseng that produce pharmacological effects are ginsenosides. Previous studies reported a memory improvement effect of a few major ginsenosides. However, the identity of specific minor ginsenosides mediating such function remains unknown. Here, we report that a minor ginsenoside F1 improves memory function in APPswe/PSEN1dE9 (APP/PS1) double-transgenic Alzheimer’s disease (AD) model mice. After 8-wk oral administration of F1 jelly, we observed that spatial working memory, but not context-dependent fear memory, was restored in AD mice. To search for a possible underlying molecular and cellular mechanism, we investigated the effect of F1 on Aβ plaque. We observed F1 administration reduced the Aβ plaque area and density in the cortex, but not in the hippocampus of AD mice. Next, we tested for the effect of F1 on the expression level of key molecules involved in learning and memory. Results from Western blot assay revealed that an abnormally reduced level of a phosphorylated form of CREB in the hippocampus of AD mice was restored to a normal level by F1 administration. Moreover, in the same animals, BDNF level was augmented in the cortex. Our results, therefore, suggest that minor ginsenoside F1 constitutes a promising target to develop therapeutic agents for AD.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a loss of neurons and severe memory impairment
In this study, we report for the first time that the administration of minor ginsenoside F1 rescues memory impairment in APP/PS1 double transgenic mice which are known as Alzheimer’s disease model mice
To find out the possible underlying mechanism, we examined an effect of F1 on Amyloid beta (Aβ) plaque in the retrosplenial cortex of AD mice
Summary
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a loss of neurons and severe memory impairment. Because AD has become a major social problem globally in an accelerating aging society [1], there has been a dramatic increase in the need for effective treatments that restore or improve memory function. Identifying a natural compound that is effective to improve memory function in AD is urgently needed. Recent researches have reported a wide range of therapeutic effects of ginseng, including tumor suppression [3, 4], anti-aging [5], After oral administration, major ginsenosides are converted into minor ginsenoside forms by hydrolyzation of the 6- and 20-glucoside bond by intestinal microflora and absorbed into the body [12]. Non-metabolized major ginsenosides have a low absorption rate in the body and are rapidly eliminated from it [15, 16]. Due to the technical difficulty to obtain a sufficient amount of minor
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