Natural 尾-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and Neuroprotective Agents from Medicinal Plants of the Genus Celastrus

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• 作者：Ruonan Ning ; Yun Lei ; Shuangzhu Liu ; Huan Wang ; Rujun Zhang ; Wei Wang ; Yingdong Zhu ; Haiyan Zhang ; Weimin Zhao
• 刊名：Journal of Natural Products
• 出版年：2015
• 出版时间：September 25, 2015
• 年：2015
• 卷：78
• 期：9
• 页码：2175-2186
• 全文大小：553K
• ISSN：1520-6025

文摘

Alzheimer鈥檚 disease (AD) is an irreversible, multifaceted, and progressive neurodegenerative disorder. Over the past 30 years, the search for anti-AD drugs has been primarily based on the cholinergic deficiency hypothesis and/or the 尾-amyloid (A尾) cascade hypothesis. In this study, we report the identification of 16 new and 38 known 尾-dihydroagarofuran-type sesquiterpenoids from Celastrus flagellaris and Celastrus angulatus. The 尾-dihydroagarofuran-type sesquiterpenoids 58, 59, 61, and 63 significantly attenuated scopolamine-induced prolonged escape latency and increased number of errors compared with the control group. At 10 渭M, 21 of the 62 tested 尾-dihydroagarofuran-type sesquiterpenoids rescued A尾_25鈥?5-induced SH-SY5Y cells from viability reduction, which increased the cell viability from 64.6% for the model to more than 74.0%. The majority of the 尾-dihydroagarofuran-type sesquiterpenoids with ester groups exhibited stronger activity than those with free hydroxy groups or without substituents at the same positions. These results identified a new chemical skeleton as drug lead for the investigation of novel therapeutic agents against AD.