Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
Int J Mol Sci. 2019 Jul 19;20(14):3538. doi: 10.3390/ijms20143538.
We explored the preventative effect of leaf (AAL) extract on memory impairment in a scopolamine (SCO)-induced cognitive deficit mouse model. Fifty-eight mice were randomly divided into six groups and orally treated with AAL extract at (50, 100, or 200 mg/kg) or tacrine (TAC) for 21 days. Memory deficits were induced by a single injection of 1 mg/kg SCO (i.p.) and memory improvement was evaluated by using behavioral tests such as the passive avoidance task and Y-maze test. The levels of cholinergic functions, neuronal cell death, reactive oxygen species, and protein expression related to hippocampal neurogenesis were examined by immunohistochemical staining and western blotting. The administration of AAL extract improved memory impairment according to increased spontaneous alternation in the Y-maze and step-through latency in passive avoidance test. AAL extract treatment increased the acetylcholine content, choline acetyltransferase, and acetylcholinesterase activity in the hippocampus of SCO-stimulated mice. In addition, AAL extract attenuated oxidative stress-induced neuronal cell death of hippocampal tissue. In terms of the regulatory mechanisms, AAL extract treatment reversed the SCO-induced decreases in the expression of Akt, phosphorylation of cAMP response element binding protein, and brain-derived neurotrophic factor. Our findings demonstrate that AAL extract has the ability to alleviate memory impairment through preventative effect on cholinergic system dysfunction and oxidative stress-related neuronal cell death in a SCO-induced memory deficit animal model. Overall, AAL may be a promising plant resource for the managing memory dysfunction due to neurodegenerative diseases, such as Alzheimer's disease (AD).
我们研究了叶（AAL）提取物对东莨菪碱（SCO）诱导的认知缺陷小鼠模型中记忆障碍的预防作用。58 只小鼠随机分为六组，分别经口给予 AAL 提取物（50、100 或 200mg/kg）或他克林（TAC）21 天。通过单次腹腔注射 1mg/kg SCO 诱导记忆障碍，并通过被动回避任务和 Y 迷宫测试等行为测试评估记忆改善情况。通过免疫组织化学染色和 Western blot 检测胆碱能功能、神经元细胞死亡、活性氧和与海马神经发生相关的蛋白质表达水平。AAL 提取物的给药根据 Y 迷宫中的自发交替和被动回避测试中的步出潜伏期的增加改善了记忆障碍。AAL 提取物处理增加了 SCO 刺激小鼠海马中的乙酰胆碱含量、胆碱乙酰转移酶和乙酰胆碱酯酶活性。此外，AAL 提取物减轻了氧化应激诱导的海马组织神经元细胞死亡。就调节机制而言，AAL 提取物处理逆转了 SCO 诱导的 Akt 表达、cAMP 反应元件结合蛋白磷酸化和脑源性神经营养因子减少。我们的研究结果表明，AAL 提取物通过预防胆碱能系统功能障碍和 SCO 诱导的记忆缺陷动物模型中与氧化应激相关的神经元细胞死亡，具有缓解记忆障碍的能力。总体而言，AAL 可能是一种有前途的植物资源，可用于管理神经退行性疾病（如阿尔茨海默病（AD））引起的记忆功能障碍。
