7,8-Dihydroxycoumarin Alleviates Synaptic Loss by Activated PI3K-Akt-CREB-BDNF Signaling in Alzheimer’s Disease Model Mice

作者：Yan Li, Yufan Jin, Junping Pan, Xiang He, Shiqian Zhong, Rongcai Zhang, LokLam Choi, Weiwei Su, Jiaxu Chen · 发表于：Journal of Agricultural and Food Chemistry · 年份：2022 · DOI：10.1021/acs.jafc.2c02140 · 被引用次数：32 · 研究领域：Alzheimer's disease research and treatments、Cholinesterase and Neurodegenerative Diseases、Medicinal Plants and Neuroprotection

High Resolution Image Download MS PowerPoint Slide Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and is clinically characterized by the impairment of memory and cognition. Accumulation of β-amyloid (Aβ) in the brain is considered as a key process in the development of AD because it impairs the synapses’ function to impair memory formation. Recent research studies have indicated that a group of edible plant-derived Thymelaeaceae compounds known as coumarin may exert particularly powerful actions on alleviating learning and memory impairment. 7,8-Dithydroxycoumarin (7,8-DHC), a bioactive component of coumarin derived from Thymelaeaceae, showed its function in neuroprotection before. In this study, we found that 7,8-DHC was able to mitigate Aβ accumulation via reducing the level of BACE1 and increasing the level of ADAM17 and ADAM10. More importantly, we found that 7,8-DHC could mitigate memory impairment, promote the dendrite branch density, and increase synaptic protein expression via activating PI3K-Akt-CREB-BDNF signaling. Hence, these results suggested that 7,8-DHC represented a novel bioactive therapeutic agent in mitigating Aβ deposition and synaptic loss in the process of treating AD.