Alzheimer's disease (AD) is a serious neuropathologic disease characterized by aggregation of amyloid-β (Aβ) peptide. Aβ-mediated oxidative stress and neuroinflammation play crucial role in the development of AD. Engeletin is a flavononol glycoside that possesses anti-inflammatory effect. However, the effects of engeletin on AD have not been investigated. In the present study, we investigated the role of engeletin in AD using an in vitro AD model. Murine microglia BV-2 cells were stimulated with Aβ1-42 (5 μM) for 24 h to induce oxidative stress and inflammation. Our results showed that treatment with engeletin suppressed Aβ1-42-induced viability reduction and lactate dehydrogenase (LDH) release in BV-2 cells. Engeletin attenuated Aβ1-42-induced oxidative stress in BV-2 cells, as proved by decreased production of reactive oxygen species (ROS) and malonaldehyde (MDA) and increased glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Aβ1-42-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were inhibited by engeletin treatment. Besides, engeletin inhibited Aβ1-42-induced production and mRNA levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6). Engeletin enhanced Aβ1-42-induced activation of Kelch-like ECH-associated protein 1 (Keap1)/nuclear transcription factor E2-related factor 2 (Nrf2) signaling pathway in BV-2 cells. Inhibition of Keap1/Nrf2 signaling pathway reversed the inhibitory effects of engeletin on Aβ1-42-induced oxidative stress and inflammation in BV-2 cells. Taken together, engeletin attenuated Aβ1-42-induced oxidative stress and inflammation in BV-2 cells via regulating the of Keap1/Nrf2 pathway. These findings indicated that engeletin might be served as a therapeutic agent for the treatment of AD.

中文翻译：

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Engeletin通过Keap1 / Nrf2途径减轻Aβ1-42诱导的氧化应激和神经炎症。

阿尔茨海默氏病（AD）是一种严重的神经病理疾病，其特征在于淀粉样β（Aβ）肽的聚集。Aβ介导的氧化应激和神经炎症在AD的发展中起关键作用。Engeletin是一种黄酮醇，具有抗炎作用。然而，尚未研究恩格列汀对AD的作用。在本研究中，我们使用体外AD模型调查了恩格列汀在AD中的作用。小鼠小胶质细胞BV-2细胞用Aβ1-42（5μM）刺激24小时，以诱导氧化应激和炎症。我们的研究结果表明，用恩格列汀进行治疗可抑制Aβ1-42诱导的活力降低和BV-2细胞中的乳酸脱氢酶（LDH）释放。Engeletin减弱BV-2细胞中Aβ1-42诱导的氧化应激，活性氧（ROS）和丙二醛（MDA）的减少以及谷胱甘肽过氧化物酶（GSH-Px）和超氧化物歧化酶（SOD）活性的增加证明了这一点。恩格列汀处理可抑制Aβ1-42诱导的一氧化氮（NO）的产生和诱导型一氧化氮合酶（iNOS）的表达。此外，恩格列汀抑制Aβ1-42诱导的肿瘤坏死因子-α（TNF-α），白介素1β（IL-1β）和白介素6（IL-6）的产生和mRNA水平。Engeletin增强BV-2细胞中Aβ1-42诱导的Kelch样ECH相关蛋白1（Keap1）/核转录因子E2相关因子2（Nrf2）信号通路的激活。Keap1 / Nrf2信号通路的抑制作用逆转了恩格列汀对Aβ1-42诱导的BV-2细胞氧化应激和炎症的抑制作用。在一起 恩格列汀通过调节Keap1 / Nrf2通路的表达来减轻BV-2细胞中Aβ1-42诱导的氧化应激和炎症。这些发现表明恩格列汀可以用作治疗AD的治疗剂。