背景:阿尔茨海默病(AD)是一种神经退行性疾病,其特征是认知能力逐渐丧失(痴呆),是主要的公共卫生问题。这里,我们的目的是研究罗莎·达马塞纳精油(RDEO)对东莨菪碱引起的健忘症大鼠模型学习和记忆功能的影响,以及乙酰胆碱酯酶(AChE)活性的变化,M1毒蕈碱乙酰胆碱受体(mAChR)表达,和脑源性神经营养因子(BDNF)在提取的脑组织中的水平。
方法:对照,健忘症(东pol碱,1mg/kg/i.p.)和治疗(RDEO,100μL/kg/p.o.或加兰他敏,1.5mg/kg/i.p.)组进行Morris水迷宫和新物体识别测试。通过ELISA测定AChE活性,蛋白质印迹法测定m1mAChR和BDNF浓度变化。此外,使用计算工具,人M1mAChR被建模为活性构象,RDEO的主要成分停靠在该受体上。
结果:根据我们的行为测试,RDEO能够减轻体内由东莨菪碱引起的学习和记忆障碍。我们的体外实验表明,观察到的积极作用与健忘大鼠大脑中AChE活性的降低以及M1mAChR和BDNF水平的增加密切相关。我们还在计算机环境中证明了RDEO的主要成分,特别是香茅醇,香叶醇,还有nerol,可以有利地容纳在活性状态人M1mAChR的变构结合袋中,并主要通过氢键和烷基-π相互作用锚定在这里。
结论:我们的研究结果为未来针对AD患者的基于RDEO的药物产品开发提供了坚实的实验基础。
BACKGROUND: Alzheimer\'s disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain-derived neurotrophic factor (BDNF) levels in the extracted brain tissues.
METHODS: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 μL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor.
RESULTS: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically -citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active-state human M1 mAChR and anchored here chiefly by hydrogen-bonding and alkyl-π interactions.
CONCLUSIONS: Our findings offer a solid experimental foundation for future RDEO-based medicinal product development for patients suffering from AD.