迷迭香酸和熊果酸可改善 Aβ诱导的阿尔茨海默病小鼠模型认知功能、突触调节和成年海马神经发生缺陷。
Rosmarinic acid and ursolic acid alleviate deficits in cognition, synaptic regulation and adult hippocampal neurogenesis in an Aβ-induced mouse model of Alzheimer's disease.
机构信息
Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
出版信息
Phytomedicine. 2021 Mar;83:153490. doi: 10.1016/j.phymed.2021.153490. Epub 2021 Jan 31.
BACKGROUND
Rosmarinus officinalis, commonly known as rosemary, is a medicinal herb that presents significant biological properties such as antimicrobial, antioxidant, anti-inflammatory, anti-diabetic and anti-depressant activities. Recent findings correlate impaired adult neurogenesis, which is crucial for the maintenance of synaptic plasticity and hippocampal functioning, synaptic regulation with the pathological hallmarks of Alzheimer's disease (AD). These observations call for the need to developing compounds that promote neurogenesis and alleviates deficits in cognition and synaptic regulation.
PURPOSE AND STUDY DESIGN
The present study was conducted to determine the proneurogenic effects of R. officinalis and its active compounds (ursolic acid and rosmarinic acid) in comparison to Donepezil in an Aβ-induced mouse model of AD.
METHODS
BALB/c mice were divided into ten groups. Half were injected with Aβ in the hippocampus through stereotaxic surgery to generate the disease groups. The other half received control injections. Each set of five groups were administered orally with vehicle, an ethanolic extract of R. officinalis, ursolic acid, rosmarinic acid or donepezil. Behavior analysis included the Morris water maze test, the novel object recognition test and the Elevated plus maze. The mice were then sacrificed and the hippocampal tissue was processed for immunohistochemistry and gene expression analysis.
RESULTS
The results show a protective effect by rosmarinic acid and ursolic acid in reversing the deficits in spatial and recognition memory as well as changes in anxiety induced by Aβ The neuronal density and the expression levels of neurogenic (Ki67, NeuN and DCX) and synaptic (Syn I, II, III, Synaptophysin and PSD-95) markers were also normalized upon treatment with rosmarinic and ursolic acid.
CONCLUSION
Our findings indicate the potential of R. officinalis and its active compounds as therapeutic agents against Aβ-induced neurotoxicity in AD.
背景
迷迭香，通常被称为迷迭香，是一种药用草药，具有显著的生物学特性，如抗菌、抗氧化、抗炎、抗糖尿病和抗抑郁活性。最近的发现与成年神经发生受损有关，成年神经发生对维持突触可塑性和海马功能至关重要，而突触调节与阿尔茨海默病（AD）的病理特征有关。这些观察结果呼吁需要开发促进神经发生和缓解认知和突触调节缺陷的化合物。
目的和研究设计
本研究旨在确定迷迭香及其活性化合物（熊果酸和迷迭香酸）在 Aβ 诱导的 AD 小鼠模型中与多奈哌齐相比的促神经发生作用。
方法
BALB/c 小鼠分为十组。一半通过立体定向手术向海马内注射 Aβ 以产生疾病组。另一半接受对照注射。每组的五组分别口服给予载体、迷迭香的乙醇提取物、熊果酸、迷迭香酸或多奈哌齐。行为分析包括 Morris 水迷宫测试、新物体识别测试和高架十字迷宫。然后处死小鼠，处理海马组织进行免疫组织化学和基因表达分析。
结果
结果表明，迷迭香酸和熊果酸具有保护作用，可逆转 Aβ 引起的空间和识别记忆缺陷以及焦虑变化。神经元密度和神经发生（Ki67、NeuN 和 DCX）和突触（Syn I、II、III、Synaptophysin 和 PSD-95）标志物的表达水平也在迷迭香酸和熊果酸治疗后得到正常化。
结论
我们的研究结果表明，迷迭香及其活性化合物具有作为治疗 AD 中 Aβ 诱导神经毒性的潜在治疗剂的潜力。
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