College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.
Arch Pharm Res. 2012 Jul;35(7):1279-86. doi: 10.1007/s12272-012-0719-1. Epub 2012 Aug 3.
Alzheimer's disease (AD) is the most prevalent cause of dementia in the elderly people. The disease is pathologically characterized by extracellular deposition of beta-amyloid peptide (Aβ), cholinergic neurodegeneration and elevation of acetylcholine esterase (AChE) activity in the affected regions. In this study, we investigated the effects of obovatol on memory dysfunction, which was caused by scopolamine. Obovatol (0.2, 0.5 and 1 mg/kg for 7 day) attenuated scopolamine (1 mg/kg, i.p.)-induced amnesia in a dose-dependent manner, as revealed by the Morris water maze test and step-through passive avoidance test. Mechanism studies exhibited that obovatol dose-dependently alleviated scopolamine-induced increase in Aβ generation and β-secretase activity in the cortex and hippocampus. Obovatol also attenuated scopolamine-induced rise in AChE activity in the cortex and hippocampus. Obovatol might rescue scopolamine-mediated impaired learning and memory function by attenuating Aβ accumulation and stabilizing cholinergic neurotransmission, which suggests that the natural compound could be a useful agent for the prevention of the development or progression of AD neurodegeneration.
阿尔茨海默病（AD）是老年人中最常见的痴呆症病因。该疾病在病理学上的特征是细胞外β-淀粉样肽（Aβ）沉积、胆碱能神经退行性变和受影响区域乙酰胆碱酯酶（AChE）活性升高。在这项研究中，我们研究了荭草素对东莨菪碱引起的记忆功能障碍的影响。荭草素（0.2、0.5 和 1 mg/kg，连续 7 天）以剂量依赖性方式减弱了东莨菪碱（1 mg/kg，腹腔注射）引起的记忆障碍，这一点通过 Morris 水迷宫测试和穿梭被动回避测试得到了揭示。机制研究表明，荭草素剂量依赖性地减轻了东莨菪碱引起的皮质和海马中 Aβ生成和β-分泌酶活性的增加。荭草素还减轻了东莨菪碱引起的皮质和海马中 AChE 活性的升高。荭草素可能通过减轻 Aβ积累和稳定胆碱能神经传递来挽救东莨菪碱介导的学习和记忆功能障碍，这表明该天然化合物可能是预防 AD 神经退行性变发展或进展的有用药物。
