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Engeletin Attenuates Aβ1–42-Induced Oxidative Stress and Neuroinflammation by Keap1/Nrf2 Pathway

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurology, Nanshi Hospital, Nanyang, 473065, China

    Zhixiong Huang, Junfeng Shi & Xinchen Zhu

  2. Department of Neurology, Lianshui People’s Hospital Affiliated to Kangda College of Nanjing Medical University, Huai’an, 223400, China

    Hu Ji

  3. Department of Neurology, The Affiliated Huai’an Hospital of Xuzhou Medical University, The Second People’s Hospital of Huai’an, No. 62 South Huaihai Road, Huai’an, 223002, China

    Zhongwen Zhi

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  1. Zhixiong Huang
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Huang, Z., Ji, H., Shi, J. et al. Engeletin Attenuates Aβ1–42-Induced Oxidative Stress and Neuroinflammation by Keap1/Nrf2 Pathway. Inflammation 43, 1759–1771 (2020). https://doi.org/10.1007/s10753-020-01250-9

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