Lan Zhang1, Xiangjian Zhang2, Cong Zhang1, Xue Bai3, Jian Zhang1, Xumeng Zhao1, Linyu Chen1, Lina Wang1, Chunhua Zhu1, Lili Cui1, Rong Chen4, Ting Zhao3, Yuan Zhao1. 1. 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 of Vascular Homeostasis, Shijiazhuang, Hebei 050000, PR China. 2. 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 of Vascular Homeostasis, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@aliyun.com. 3. Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China. 4. Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang, Hebei 050000, PR China.
Abstract
BACKGROUND: Post-ischemic oxidative stress and inflammation play pivotal roles in the pathogenesis of ischemic stroke and may represent therapeutic targets. Nobiletin (NOB) has been reported to elicit a variety of biological effects through its anti-oxidant and anti-inflammatory properties. Our previous study has demonstrated the beneficial effect of NOB in ischemic stroke, but the underlying mechanisms remain poorly defined. We therefore further investigated the role of NOB in cerebral ischemia and its potential mechanisms. METHODS: Adult male Sprague-Dawley rats were randomly assigned to five groups: Sham (sham-operated+0.05% Tween-80), permanent middle cerebral artery occlusion (pMCAO+0.9% saline), Vehicle (pMCAO+0.05% Tween-80), NOB-L (pMCAO+NOB 10mg/kg) and NOB-H (pMCAO+NOB 25mg/kg) groups. Rats were pre-administered intraperitoneally once daily for 3 days prior to ischemia and then received once again immediately after surgery. Neurological deficit, brain edema and infarct volume were evaluated at 24h after stroke. Immunohistochemistry, western blot and RT-qPCR were used to detect the expression of Nrf2, HO-1, SOD1, NF-κB and MMP-9. SOD1, GSH and MDA were measured by spectrophotometer. RESULTS: Compared with Vehicle group, neurological deficits and brain edema were relieved in NOB-H group, infarct volume was lessened in both NOB-L and NOB-H groups (P<0.05). NOB significantly increased the expression of Nrf2, HO-1, SOD1 and GSH, while decreased the levels of NF-κB, MMP-9 and MDA (P<0.05). CONCLUSION: NOB may have a neuroprotective effect on cerebral ischemia, and this protection may be through upregulating Nrf2, HO-1 and downregulating NF-κB expression.
BACKGROUND: Post-ischemic oxidative stress and inflammation play pivotal roles in the pathogenesis of ischemic stroke and may represent therapeutic targets. Nobiletin (NOB) has been reported to elicit a variety of biological effects through its anti-oxidant and anti-inflammatory properties. Our previous study has demonstrated the beneficial effect of NOB in ischemic stroke, but the underlying mechanisms remain poorly defined. We therefore further investigated the role of NOB in cerebral ischemia and its potential mechanisms. METHODS: Adult male Sprague-Dawley rats were randomly assigned to five groups: Sham (sham-operated+0.05% Tween-80), permanent middle cerebral artery occlusion (pMCAO+0.9% saline), Vehicle (pMCAO+0.05% Tween-80), NOB-L (pMCAO+NOB 10mg/kg) and NOB-H (pMCAO+NOB 25mg/kg) groups. Rats were pre-administered intraperitoneally once daily for 3 days prior to ischemia and then received once again immediately after surgery. Neurological deficit, brain edema and infarct volume were evaluated at 24h after stroke. Immunohistochemistry, western blot and RT-qPCR were used to detect the expression of Nrf2, HO-1, SOD1, NF-κB and MMP-9. SOD1, GSH and MDA were measured by spectrophotometer. RESULTS: Compared with Vehicle group, neurological deficits and brain edema were relieved in NOB-H group, infarct volume was lessened in both NOB-L and NOB-H groups (P<0.05). NOB significantly increased the expression of Nrf2, HO-1, SOD1 and GSH, while decreased the levels of NF-κB, MMP-9 and MDA (P<0.05). CONCLUSION:NOB may have a neuroprotective effect on cerebral ischemia, and this protection may be through upregulating Nrf2, HO-1 and downregulating NF-κB expression.