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

Alzheimer's disease (AD) is a serious neuropathologic disease characterized by aggregation of amyloid-beta (A beta) peptide. A beta-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 A beta 1-42 (5 mu M) for 24 h to induce oxidative stress and inflammation. Our results showed that treatment with engeletin suppressed A beta 1-42-induced viability reduction and lactate dehydrogenase (LDH) release in BV-2 cells. Engeletin attenuated A beta 1-42-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. A beta 1-42-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were inhibited by engeletin treatment. Besides, engeletin inhibited A beta 1-42-induced production and mRNA levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6). Engeletin enhanced A beta 1-42-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 A beta 1-42-induced oxidative stress and inflammation in BV-2 cells. Taken together, engeletin attenuated A beta 1-42-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.