title: Sinomenine Provides Neuroprotection in Model of Traumatic Brain Injury via the Nrf2-ARE Pathway.
abstract: The neuroprotective effect of sinomenine (SIN) has been demonstrated in several brain injury models. However, its role and molecular mechanism in traumatic brain injury (TBI) remain unknown. In this study, we investigated the neuroprotective effects of SIN in the weight-drop model of TBI in male ICR mice. Mice were randomly divided into the sham and TBI groups, SIN (10 mg/kg, 30 mg/kg and 50 mg/kg, administered intraperitoneally) or equal volume of vehicle was given at 30 min after TBI. Treatment with 30 mg/kg SIN significantly improved motor performance and alleviated cerebral edema. However, treatment with 10 mg/kg or 50 mg/kg SIN did not exhibit a better outcome. Therefore, we chose 30 mg/kg SIN for our subsequent experiments. SIN significantly increased the expression of Bcl-2 and decreased that of cleaved caspase-3, indicating that SIN is anti-apoptotic. This was confirmed by the observation that SIN-treated animals had fewer apoptotic neurons. Cortical malondialdehyde content, glutathione peroxidase (GPx) activity and superoxide dismutase (SOD) activity were restored in the group that received SIN. Furthermore, Western blot and immunofluorescence experiments showed that SIN enhanced the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus. SIN administration also significantly upregulated the expression of the downstream factors heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 at pre- and post-transcriptional levels. Together, these data demonstrate that SIN exerts a neuroprotective effect in a model of TBI, possibly by activating the Nrf2-antioxidant response element (ARE) pathway.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Clinical Medical College of Southern Medical University (Guangzhou) Nanjing, China.
authors.forename: Youqing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Clinical Medical College of Southern Medical University (Guangzhou) Nanjing, China.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Clinical Medical College of Southern Medical University (Guangzhou) Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, Clinical Medical College of Southern Medical University (Guangzhou) Nanjing, China.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Mengliang
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Pan
keywords: neuroprotection; nuclear factor erythroid 2-related factor 2; reactive oxygen species; sinomenine; traumatic brain injury