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黄秋葵的类黄酮可抵御氧化应激、神经炎症,并可恢复 Aβ 诱导的阿尔茨海默病小鼠模型中的 BDNF 水平。

The flavonoids of okra insulates against oxidative stress, neuroinflammation and restores BDNF levels in Aβ induced mouse model of Alzheimer's disease.

机构信息

School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.

School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016, China.

出版信息

Exp Gerontol. 2021 May;147:111263. doi: 10.1016/j.exger.2021.111263. Epub 2021 Jan 28.

DOI:10.1016/j.exger.2021.111263
PMID:33516906
Abstract

Okra (Abelmoschus esculentus [L.] Moench.) has been used as a natural drug in East or West Africa for many centuries, as well as consumed in most areas of the world as a tropical vegetable. The study aimed to evaluate whether the flavonoids of okra fruit (FOF) administration influence Aβ-induced learning and memory impairment, and explore the underlying mechanisms. The Y-maze task and the Morris water maze test were used for evaluating cognition processes. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) were detected by ELISA kits. The expressions of nuclear factor kappa-light chain-enhancer of activated B (NF-κB), brain-derived neurotrophic factor (BDNF), cAMP-response element-binding protein (CREB), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), glycogen synthase kinase-3β (GSK-3β) were studied by western blot. Histopathological changes were observed by H.E. straining. The results showed that intracerebroventricular injection of Aβ was effective in producing memory deficits in mice. Besides, Aβ exposure could significantly increase the levels of NF-κB, TNF-α, IL-1β, and decreased T-AOC, the activities of SOD and GSH-Px in the hippocampus and cortex. Furthermore, the level of BDNF was also reduced, accompanied by down-regulated CREB/ERK and PI3K/AKT/GSK-3β signaling pathways in the hippocampus and cortex. Nevertheless, chronic administration of FOF (100 or 300 mg/kg, i.g.) significantly prevented Aβ-induced behavioral and biochemical alterations. It also suggested that FOF could improve the cognitive deficits in AD-like model mice, which might be mediated by regulation of BDNF levels in cortex and hippocampus and up-regulating of CREB/ERK and PI3K/AKT/GSK3β pathways, as well as alleviation of oxidative stress and neuroinflammation.

摘要

奥克瓜(Abelmoschus esculentus [L.] Moench.)作为一种天然药物,在东非和西非被使用了数个世纪,并且在世界上的大多数地区,它也被作为一种热带蔬菜被食用。本研究旨在评估奥克瓜果实中的类黄酮(FOF)的给药是否会影响 Aβ 诱导的学习和记忆障碍,并探索其潜在机制。Y 迷宫任务和 Morris 水迷宫测试被用于评估认知过程。通过 ELISA 试剂盒检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)和谷胱甘肽过氧化物酶(GSH-Px)的水平。通过 Western blot 研究核因子 kappa-轻链增强子的激活 B(NF-κB)、脑源性神经营养因子(BDNF)、cAMP 反应元件结合蛋白(CREB)、细胞外信号调节激酶(ERK)、磷脂酰肌醇 3 激酶(PI3K)、蛋白激酶 B(AKT)、糖原合成酶激酶-3β(GSK-3β)的表达。通过 H.E.染色观察组织病理学变化。结果表明,侧脑室注射 Aβ可有效导致小鼠记忆缺陷。此外,Aβ 暴露可显著增加海马和皮质中 NF-κB、TNF-α、IL-1β 的水平,降低 T-AOC、SOD 和 GSH-Px 的活性。此外,BDNF 的水平也降低了,伴随着海马和皮质中 CREB/ERK 和 PI3K/AKT/GSK-3β 信号通路的下调。然而,FOF(100 或 300mg/kg,ig)的慢性给药显著预防了 Aβ 诱导的行为和生化改变。这也表明 FOF 可以改善 AD 样模型小鼠的认知缺陷,这可能是通过调节皮质和海马中的 BDNF 水平以及上调 CREB/ERK 和 PI3K/AKT/GSK3β 通路,以及缓解氧化应激和神经炎症来实现的。

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