Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

作者：Han Wang, Xiaoming Zhou, Lingyun Wu, Guangjie Liu, Weidong Xu, Xiangsheng Zhang, Yongyue Gao, Tao Tao, Yan Zhou, Yue Lu, Juan Wang, Chu-Lei Deng, Zong Zhuang, Chun‐Hua Hang, Wei Li · 发表于：Journal of Neuroinflammation · 年份：2020 · DOI：10.1186/s12974-020-01863-9 · 被引用次数：217 · 研究领域：Genomics, phytochemicals, and oxidative stress、Traumatic Brain Injury and Neurovascular Disturbances、Chemotherapy-induced organ toxicity mitigation

Abstract Background Aucubin (Au), an iridoid glycoside from natural plants, has antioxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in an H 2 O 2 -induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model. Methods In vitro experiments, the various concentrations of Au (50 μg/ml, 100 μg/ml, or 200 μg/ml) were added in culture medium at 0 h and 6 h after neurons stimulated by H 2 O 2 (100 μM). After exposed for 12 h, neurons were collected for western blot (WB), immunofluorescence, and M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In vivo experiments, Au (20 mg/kg or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling. Brain water content, neurological deficits, and cognitive functions were measured at specific time, respectively. Cortical tissue around focal trauma was collected for WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry, and enzyme linked immunosorbent assay (ELISA) at 72 h after TBI. RNA interference experiments were performed to determine the effects of nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with Au (40 mg/kg) treatment. Mice were intracerebroventricularly administrated with lentivirus at 72 h before TBI establish...