Jian Zhang1, Baosheng Fu2, Xiangjian Zhang3, Lan Zhang1, Xue Bai1, Xumeng Zhao1, Linyu Chen1, Lili Cui1, Chunhua Zhu1, Lina Wang1, Yuan Zhao1, Ting Zhao1, Xiaolu Wang4. 1. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. 2. Department of Geriatrics, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. 3. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@aliyun.com. 4. Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China.
Abstract
UNLABELLED: Oxidative damage plays a detrimental role in the pathophysiology of cerebral ischemia and may represent a therapeutic target. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the coordinated expression of the important antioxidant and detoxification genes through a promotor sequence termed the antioxidant response element. Bicyclol has been proved to elicit a variety of biological effects through its antioxidant and anti-inflammatory properties. But the underlying mechanisms are poorly understood. In this study, the role of bicyclol in cerebral ischemia and its potential mechanism were investigated. METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: MCAO (middle cerebral artery occlusion), Vehicle (MCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50mg/kg), By-H (Vehicle+bicyclol 100mg/kg) and Sham operated groups. Bicyclol was administered intragastrically once a day for 3 consecutive days; after 1h of bicyclol pretreatment on the third day, rat ischemic stroke was induced by MCAO. Neurological deficit, infarct volume, and brain edema were detected at 24h after stroke. Western blot and RT-qPCR were used to measure the expression of Nrf2, HO-1 and SOD1. MDA was detected by the spectrophotometer. RESULTS: Compared with MCAO group, By-H group significantly ameliorated neurological deficit, lessened the infarct volume and brain edema, increased the expression of Nrf2, HO-1 and SOD1 (P<0.05), and decreased the content of MDA (P<0.05). CONCLUSIONS: Bicyclol protected the rat brain from ischemic damage caused by MCAO, and this effect may be through the upregulation of the transcription factor Nrf2 expression.
UNLABELLED: Oxidative damage plays a detrimental role in the pathophysiology of cerebral ischemia and may represent a therapeutic target. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the coordinated expression of the important antioxidant and detoxification genes through a promotor sequence termed the antioxidant response element. Bicyclol has been proved to elicit a variety of biological effects through its antioxidant and anti-inflammatory properties. But the underlying mechanisms are poorly understood. In this study, the role of bicyclol in cerebral ischemia and its potential mechanism were investigated. METHODS: Male Sprague-Dawley rats were randomly assigned to five groups: MCAO (middle cerebral artery occlusion), Vehicle (MCAO+0.5% sodium carboxymethylcellulose), By-L (Vehicle+bicyclol 50mg/kg), By-H (Vehicle+bicyclol 100mg/kg) and Sham operated groups. Bicyclol was administered intragastrically once a day for 3 consecutive days; after 1h of bicyclol pretreatment on the third day, ratischemic stroke was induced by MCAO. Neurological deficit, infarct volume, and brain edema were detected at 24h after stroke. Western blot and RT-qPCR were used to measure the expression of Nrf2, HO-1 and SOD1. MDA was detected by the spectrophotometer. RESULTS: Compared with MCAO group, By-H group significantly ameliorated neurological deficit, lessened the infarct volume and brain edema, increased the expression of Nrf2, HO-1 and SOD1 (P<0.05), and decreased the content of MDA (P<0.05). CONCLUSIONS:Bicyclol protected the rat brain from ischemic damage caused by MCAO, and this effect may be through the upregulation of the transcription factor Nrf2 expression.