Department of Integrative Biological Sciences and Industry & Convergence Research Center for Natural Products, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, 05006, Republic of Korea.
Natural Product Research Center, Korea Institute of Science and Technology, 679 Saimdang-ro, Gangneung, 25451, Gangwon-do, Republic of Korea.
Mol Neurobiol. 2024 Dec;61(12):10845-10860. doi: 10.1007/s12035-024-04242-0. Epub 2024 May 27.
Dementia is a syndrome exhibiting progressive impairments on cognition and behavior beyond the normal course of aging, and Alzheimer's disease (AD) is one of the neurodegenerative diseases known to cause dementia. We investigated the effect of KGC07EH, the 30% ethanol extract of Euonymus hamiltonianus, against amyloid-β (Aβ) production and cognitive dysfunction in dementia models. KGC07EH was treated on Hela cells expressing the Swedish mutant form of amyloid precursor protein (APP), and the AD triple transgenic (3× TG) mice were given KGC07EH orally during 11-14 months of age (100 and 300 mg/kg/day). SH-SY5Y cell line was used to test KGC07EH on scopolamine-induced elevation of acetylcholinesterase (AChE) activity. ICR mice were intraperitoneally injected with scopolamine, and KGC07EH was administered orally (50, 100, and 200 mg/kg/day) for 4 weeks. KGC07EH treatment decreased Aβ, sAPPβ-sw, and sAPPβ-wt levels and APP protein expressions while sAPPα was increased in Swedish mutant-transfected HeLa cells. KGC07EH treatment also significantly reduced the accumulation of Aβ plaques and tau tangles in the brain of 3× TG mice as well as improving the cognitive function. In SH-SY5Y cells cultured with scopolamine, KGC07EH dose-dependently attenuated the increase of AChE activity. KGC07EH also improved scopolamine-induced learning and memory impairment in scopolamine-injected mice, and in their cerebral cortex and hippocampus, the expression levels of p-ERK, p-CREB, p-Akt, and BDNF were attenuated. KGC07EH inhibits APP processing and Aβ production both in vitro and in vivo, while enhancing acetylcholine signaling and cognitive dysfunction which are the major symptoms of dementia.
痴呆症是一种表现为认知和行为障碍的综合征，超出了正常衰老的范围，而阿尔茨海默病（AD）是已知导致痴呆症的神经退行性疾病之一。我们研究了 KGC07EH（杠柳酮醇-7-O-β-D-葡萄糖醛酸苷，Euonymus hamiltonianus 的 30%乙醇提取物）对痴呆症模型中淀粉样蛋白-β（Aβ）产生和认知功能障碍的影响。KGC07EH 作用于表达淀粉样前体蛋白（APP）瑞典突变体的 Hela 细胞，AD 三转基因（3×TG）小鼠在 11-14 月龄时口服 KGC07EH（100 和 300mg/kg/天）。SH-SY5Y 细胞系用于测试 KGC07EH 对东莨菪碱诱导的乙酰胆碱酯酶（AChE）活性升高的影响。ICR 小鼠腹腔注射东莨菪碱，KGC07EH 口服给药（50、100 和 200mg/kg/天）4 周。KGC07EH 处理降低了 Aβ、sAPPβ-sw 和 sAPPβ-wt 水平和 APP 蛋白表达，而 sAPPα 在转染瑞典突变体的 HeLa 细胞中增加。KGC07EH 处理还显著减少了 3×TG 小鼠大脑中 Aβ 斑块和 tau 缠结的积累，并改善了认知功能。在东莨菪碱培养的 SH-SY5Y 细胞中，KGC07EH 呈剂量依赖性减弱 AChE 活性的增加。KGC07EH 还改善了东莨菪碱注射小鼠的学习和记忆障碍，以及其大脑皮层和海马中的 p-ERK、p-CREB、p-Akt 和 BDNF 的表达水平。KGC07EH 抑制 APP 处理和体内外 Aβ 产生，同时增强乙酰胆碱信号传导和认知功能障碍，这是痴呆症的主要症状。
