Senkyunolide I protects rat brain against focal cerebral ischemia-reperfusion injury by up-regulating p-Erk1/2, Nrf2/HO-1 and inhibiting caspase 3.

Oxidative damage and apoptosis are critical factors contributing to neuronal death during a stroke. The aim of the present study was to evaluate the neuroprotective effects of senkyunolide I (SEI) on focal cerebral ischemia-reperfusion (I/R) injury in rats, and investigate the underlying mechanisms. Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (tMCAO) for 2h, followed by 24h reperfusion, and then randomly assigned into four groups: Sham (sham-operated), Vehicle (tMCAO +normal saline), SEI-L (tMCAO +SEI 36 mg/kg) and SEI-H (tMCAO +SEI 72 mg/kg) groups. SEI was administered intravenously, 15 min after occlusion. Neurological deficit, brain edema and infarct volume were detected after 24h of reperfusion. Histological structures of cortices and hippocampus were observed by hematoxylin and eosin staining. Biochemical indexes in the cortex were assayed by colorimetry. The impact of SEI on the Nrf2-ARE-interaction was assayed using a luciferase reporter gene. Western blotting was performed to analysis the expressions of proteins related to anti-oxidation and apoptosis. SEI administration significantly ameliorated the neurological deficit, reduced the infarct volume and brain edema, reversed the cerebral morphologic damage, decreased the levels of MDA and increased the activities of superoxide dismutase. Furthermore, the high dose SEI could significantly activate the Nrf2/ARE pathway by up-regulating the phosphorylation of Erk1/2 and inducing Nrf2 nuclear translocation with enhanced HO-1 and NQO1 expressions. Additionally, treatment with SEI remarkably promoted the ratio of Bcl-2/Bax and inhibited the expressions of cleaved caspase 3 and caspase 9. These results suggest that the neuroprotective mechanisms of SEI are associated with its anti-oxidation and anti-apoptosis properties.

Hu Y ，Duan M ，Liang S ，Wang Y ，Feng Y ... -  《-》

Neohesperidin attenuates cerebral ischemia-reperfusion injury via inhibiting the apoptotic pathway and activating the Akt/Nrf2/HO-1 pathway.

Wang JJ ，Cui P 《-》

Resveratrol pretreatment attenuates cerebral ischemic injury by upregulating expression of transcription factor Nrf2 and HO-1 in rats.

Ren J ，Fan C ，Chen N ，Huang J ，Yang Q ... -  《-》

Protective effect of Sheng-Nao-Kang decoction on focal cerebral ischemia-reperfusion injury in rats.

Sheng-Nao-Kang decoction (SNK), a modified traditional Chinese medicine (TCM), has been used clinically for the treatment of acute and chronic cerebrovascular related diseases. To evaluate the protective effect of SNK on focal cerebral ischemia-reperfusion (I/R) injury in rats and investigate the underlying mechanisms. Focal cerebral I/R injury in rats was induced by middle cerebral artery occlusion (MCAO) for 2h followed by reperfusion for 24h. Adult male Sprague-Dawley (SD) rats were randomly divided into six kinds of groups: Sham group; I/R group; SNK-treated groups at doses of 0.7 g/kg, 1.4 g/kg and 2.8 g/kg; and nimodipine (NMP)-treated group. The recoveries of neurological function in rats were estimated by neurological defect scoring and 2,3,5-triphenyltetrazolium chloride (TTC) staining after 24h reperfusion. Various biochemical indexes in serum were assayed by colorimetry, including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), inducible nitric oxide synthase (iNOS) and total nitric oxide synthase (TNOS). Histological structures of the brain in rats were observed by hematoxylin and eosin (H&E) staining. Immunohistochemistry was performed to detect the caspase-3 protein content in rats. SNK administration significantly reduced the neurological defect scores and lessened the cerebral infarction volume. The treatment of SNK lowered MDA content, up-regulated SOD and GSH-Px levels, down-regulated iNOS and TNOS levels in serum. Furthermore, histological examination indicated that dense neuropil and largely surviving neurons were seen in SNK-treated rats. SNK administration restrained the expression of caspase-3 positive protein significantly. The results suggest that SNK demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The protective mechanisms of SNK are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of iNOS and TNOS.

Chen L ，Zhao Y ，Zhang T ，Dang X ，Xie R ，Li Z ，Li Y ，Li Y ，Zhao W ，Song H ... -  《-》

Bicyclol upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia.

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. 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. 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). 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.

Zhang J ，Fu B ，Zhang X ，Zhang L ，Bai X ，Zhao X ，Chen L ，Cui L ，Zhu C ，Wang L ，Zhao Y ，Zhao T ，Wang X ... -  《-》