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白杨素载药脂质核纳米囊泡改善β-淀粉样蛋白诱导的老年雌性小鼠神经行为改变。

Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by β-amyloid in aged female mice.

机构信息

Programa de Pós-Graduação em Bioquímica, Universidade Federal do Pampa, UNIPAMPA, Uruguaiana, RS 97500-970, Brazil.

Programa de Pós-Graduação em Bioquímica, Universidade Federal do Pampa, UNIPAMPA, Uruguaiana, RS 97500-970, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, UNIPAMPA, Uruguaiana, RS 97500-970, Brazil.

出版信息

Behav Brain Res. 2020 Jul 15;390:112696. doi: 10.1016/j.bbr.2020.112696. Epub 2020 May 15.

DOI:10.1016/j.bbr.2020.112696
PMID:32417280
Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a clinically and progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Some studies showed that chrysin has antioxidant and anti-inflammatory properties. However, your bioavailability is relatively low. Therefore, the present study was designed to investigate the effects of chrysin loaded lipid-core nanocapsules (LNCs) on neurochemical and behavioral changes in a model of AD induced by β-amyloid (Aβ) peptide in aged female mice. For this purpose, aged female mice received free chrysin (FC) (5 mg/kg, per oral, p.o.) or chrysin loaded LNCs (C1-LNC and C5-LNC) (1 or 5 mg/kg, p.o.) for 14 days after Aβ administration (400 pmol, i.c.v.). Aβ induced significant impairments on memory and learning (morris water maze task, object recognition and step-down-type passive avoidance), also caused oxidative stress, reduced the levels of brain-derived neurotrophic factor (BDNF), increased neuroinflammation in prefrontal cortex and hippocampus of aged animals. Thus, C1-LNC and C5-LNC displayed significant effect against Aβ₁₄ via attenuation of oxidative stress and neuroinflammation, modulation of neurochemical and behavioral changes in a model of AD. These results point to chrysin loaded LNCs (mainly C5-LNC) can be a promising biomedical tool and a new therapeutic approach for treatment and prevention of AD.

摘要

阿尔茨海默病(AD)是一种神经退行性疾病,其特征是临床和进行性认知功能丧失、神经精神和行为障碍。一些研究表明,白杨素具有抗氧化和抗炎特性。然而,其生物利用度相对较低。因此,本研究旨在探讨白杨素负载脂质核纳米囊(LNC)对β-淀粉样肽(Aβ)诱导的老年雌性小鼠 AD 模型中神经化学和行为变化的影响。为此,在 Aβ给药后(400 pmol,icv),老年雌性小鼠接受游离白杨素(FC)(5 mg/kg,口服,po)或白杨素负载 LNC(C1-LNC 和 C5-LNC)(1 或 5 mg/kg,po)14 天。Aβ 导致记忆和学习能力显著受损(莫里斯水迷宫任务、物体识别和下台阶式被动回避),还导致氧化应激,降低脑源性神经营养因子(BDNF)水平,增加老年动物前额叶皮层和海马体的神经炎症。因此,C1-LNC 和 C5-LNC 通过减轻氧化应激和神经炎症,调节 AD 模型中的神经化学和行为变化,对 Aβ₁₄ 显示出显著的作用。这些结果表明,白杨素负载 LNC(主要是 C5-LNC)可能是一种有前途的生物医学工具和治疗 AD 的新方法。

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