title: Luteolin provides neuroprotection in models of traumatic brain injury via the Nrf2-ARE pathway.
abstract: Luteolin has recently been proven to exert neuroprotection in a variety of neurological diseases; however, its roles and the underlying mechanisms in traumatic brain injury are not fully understood. The present study was aimed to investigate the neuroprotective effects of luteolin in models of traumatic brain injury (TBI) and the possible role of the Nrf2-ARE pathway in the putative neuroprotection. A modified Marmarou׳s weight-drop model in mice and the scratch model in mice primary cultured neurons were used to induce TBI. We determined that luteolin significantly ameliorated secondary brain injury induced by TBI, including neurological deficits, brain water content, and neuronal apoptosis. Furthermore, the level of malondialdehyde (MDA) and the activity of glutathione peroxidase (GPx) were restored in the group with luteolin treatment. in vitro studies showed that luteolin administration lowered the intracellular reactive oxygen species (ROS) level and increased the neuron survival. Moreover, luteolin enhanced the translocation of Nrf2 to the nucleus both in vivo and in vitro, which was proved by the results of Western blot, immunohistochemistry, and electrophoretic mobility shift assay (EMSA). Subsequently upregulation of the expression of the downstream factors such as heme oxygenase 1 (HO1) and
  quinone oxidoreductase 1 (NQO1) was also examined. However, luteolin treatment failed to provide neuroprotection after TBI in Nrf2(-/-) mice. Taken together, these in vivo and in vitro data demonstrated that luteolin provided neuroprotective effects in the models of TBI, possibly through the activation of the Nrf2-ARE pathway.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People׳s Republic of China. Electronic address: njhdwang@hotmail.com.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Chunxi
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Wuting
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, People׳s Republic of China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D061251:Primary Cell Culture; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014867:Water / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D014867:Water; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D047311:Luteolin
keywords: Luteolin; Neuroprotection; Nrf2; Traumatic brain injury