ABSTRACT
BACKGROUND: As one major symptom of Alzheimer's disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD. METHODS: mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK-/-) mice. Animals' cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation. RESULTS: Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK-/- mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists. CONCLUSIONS: Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.
Subject(s)
Alzheimer Disease , Amnesia, Anterograde , Cholecystokinin , Mice, Transgenic , Receptor, Cholecystokinin B , Animals , Mice , Aging/drug effects , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amnesia, Anterograde/drug therapy , Cholecystokinin/metabolism , Disease Models, Animal , Entorhinal Cortex/drug effects , Entorhinal Cortex/metabolism , Hippocampus/metabolism , Hippocampus/drug effects , Long-Term Potentiation/drug effects , Mice, Inbred C57BL , Mice, Knockout , Receptor, Cholecystokinin B/genetics , Receptor, Cholecystokinin B/agonists , Receptor, Cholecystokinin B/deficiencyABSTRACT
Astragalus is a popular Materia Medica in China, and it could be applied in the treatment of various diseases. It contains a variety of chemically active ingredients, such as saponins, flavonoids, and polysaccharides. Plant-derived bioactive chemicals are considered natural, safe, and beneficial. Among the infinite plant-identified and isolated molecules, flavonoids have been reported to have positive effects on human health. Calycosin is the most important active flavonoid substance identified predominantly within this medicinal plant. In recent years, calycosin has been reported to have anticancer, antioxidative, immune-modulatory, and estrogenic-like properties. This review collected recent relevant literatures on calycosin and summarized its potential pharmaceutical properties and working mechanism involved, which provided solid basis for future clinical research.