The protection by octreotide against experimental ischemic stroke: up-regulated transcription factor Nrf2, HO-1 and down-regulated NF-κB expression.

Inflammatory and oxidative damage play a pivotal role in cerebral ischemic pathogenesis and may represent a therapeutic target. Octreotide (OCT) has been proved to elicit a variety of biological effects through its anti-inflammatory and anti-oxidant properties in the treatment of severe acute pancreatitis and ischemia-reperfusion injury in retina and intestine. However little is known regarding the effect of OCT in ischemic stroke. Here, we designed this study to investigate the protective effect of OCT in ischemic stroke and explore the potential underlying mechanisms. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (pMCAO) and randomly divided into four groups: Sham (sham-operated), MCAO (pMCAO+0.9% saline), OCT-L (pMCAO+OCT 50μg/kg) and OCT-H (pMCAO+OCT 100μg/kg) groups. OCT was administered intraperitoneally immediately after stroke. Neurological deficit scores, infarct volume and brain water content were measured at 24h after stroke. Immunohistochemical staining and western blot were used to analyze the expressions of Nrf2, HO-1 and NF-κB. SOD and MDA were measured by spectrophotometer. Compared with MCAO group, OCT significantly alleviated neurological deficit, lessened infarct volume and brain edema (P<0.05), upregulated the expression of Nrf2, HO-1 and SOD (P<0.05), and decreased the expression of NF-κB and MDA (P<0.05). OCT protected the brain against cerebral ischemic damage; this effect may be through upregulation of transcription factor Nrf2, HO-1 and downregulation of NF-κB expression.

Chen L ，Wang L ，Zhang X ，Cui L ，Xing Y ，Dong L ，Liu Z ，Li Y ，Zhang X ，Wang C ，Bai X ，Zhang J ，Zhang L ，Zhao X ... -  《-》

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 ... -  《-》

Paeonol pretreatment attenuates cerebral ischemic injury via upregulating expression of pAkt, Nrf2, HO-1 and ameliorating BBB permeability in mice.

Oxidative damage plays a pivotal role in the pathogenesis of cerebral ischemic stroke and may represent a target for treatment. Our previous studies have proved that nuclear factor E2-related factor 2 (Nrf2) and its downstream genes served as a key mechanism for protection against oxidative stress. Paeonol (PN) is reputed to possess a broad range of therapeutic properties probably by virtue of its antioxidative ability. However little is elucidated regarding the underlying mechanisms in ischemic stroke. The aim of this study was to explore PNs effect in ischemic injury and the role of the pAkt, Nrf2 and hemeoxygenase-1 (HO-1) in the mice brains of permanent middle cerebral artery occlusion (pMCAO). Male CD-1 mice were subjected to pMCAO and randomly divided into five groups: Sham (sham-operated+0.9% saline), pMCAO (pMCAO+0.9% saline), Vehicle (pMCAO+vehicle), PN-L (pMCAO+PN 30 mg/kg) and PN-H (pMCAO+PN 60 mg/kg) groups. PN was pre-administered intragastrically once daily for 3 days and with the last administration at 30 min before the operation in the fourth day. Neurological deficit scores, brain water content and infarct volume were measured at 24h after pMCAO. Western blot and qRT-PCR were employed to determine the expressions of pAkt, Nrf2, HO-1 and claudin-5. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by spectrophotometer. Compared with Vehicle group, PN significantly alleviated neurological deficit, infarct volume and brain edema (P<0.05), upregulated the expression of pAkt, Nrf2, HO-1 and SOD (P<0.05), decreased the level of MDA (P<0.05). Meanwhile, the expression of claudin-5 was also enhanced. PN reduced ischemic brain injury after pMCAO; this effect may be accompanied with upregulation of pAkt, Nrf2, HO-1 and ameliorating BBB permeability.

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

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

Yang C ，Zhang X ，Fan H ，Liu Y ... -  《-》

Luteolin downregulates TLR4, TLR5, NF-κB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia.

Inflammatory damage is known to be involved in ischemic stroke. Luteolin has been proved to elicit a series of biologic effects through its anti-inflammatory property in multiple sclerosis and rheumatoid arthritis. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigate the potential neuroprotective role of luteolin in ischemic stroke and the underlying mechanisms. Male Sprague-Dawley rats were subjected to pMCAO and luteolin was administered intraperitoneally immediately after surgery, then once daily thereafter. Neurological deficit, infarct volume, and brain water content were measured at 24 h and 72 h after stroke. The expression of TLR4, TLR5, and NF-κB were measured by real-time PCR, immunohistochemical staining (IHC), and Western blot. P38MAPK and extracellular signal-regulated kinase (ERK) were detected by IHC, and Western blot. Compared with pMCAO group, luteolin significantly alleviated neurological deficit, decreased infarct volume and suppressed edema after ischemic stroke, which were accompanied with decreased expression of TLR4, TLR5, NF-κB and p-p38MAPK. Meanwhile, luteolin activated the expression of p-ERK1/2 (P<0.05). Luteolin protected the brain from the damage caused by pMCAO, and this effect may be through downregulation of TLR4, TLR5, NF-κB, p38MAPK and upregulation of ERK expression.

Qiao H ，Zhang X ，Zhu C ，Dong L ，Wang L ，Zhang X ，Xing Y ，Wang C ，Ji Y ，Cao X ... -  《-》