Chaohui Wang

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

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia: up-regulated pAkt, pGSK and pCREB, down-regulated NF-κB expression, ameliorated BBB permeability.

BACKGROUND Berberine (BBR) has gained attention for its vast beneficial biological effects through immunomodulation, anti-inflammatory and anti-apoptosis properties. Inflammatory and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The aim of this study was to explore BBRs effect in ischemic injury and the role of the Akt/GSK (glycogen synthase kinase) signaling cascade in mediating the anti-apoptosis and anti-inflammatory effects in the rat brain of permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats were subjected to pMCAO and randomly assigned into four groups: Sham (sham-operated) group, pMCAO (pMCAO+0.9% saline) group, BBR-L (pMCAO+BBR 10 mg/kg) and BBR-H (pMCAO+BBR 40 mg/kg) group. BBR was administered immediately after pMCAO and the neuroprotection was detected. Phospho-Akt (pAkt), phospho-glycogen synthase kinase 3-β (pGSK3β), phospho-cAMP response element binding protein (pCREB), nuclear factor-kappa B (NF-κB) and claudin-5 in ischemic cerebral cortex were detected by immunohistochemistry, reverse transcription-polymerase chain reaction and western blotting. Compared with pMCAO group, BBR dramatically lessened neurological deficits scores, brain water contents and infarct sizes, upregulated the expression of pAkt, pGSK3β, pCREB and claudin-5, and decreased the nuclear accumulation of NF-κB (P<0.05) in ischemic brain. The results showed that BBR reduced ischemic brain injury after pMACO, and this effect may be via the increasing the activation of Akt/GSK signaling and claudin-5, and decreasing NF-κB expression.

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

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Protection by silibinin against experimental ischemic stroke: Up-regulated pAkt, pmTOR, HIF-1α and Bcl-2, down-regulated Bax, NF-κB expression

Inflammation and apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Silibinin has been proved to elicit a variety of biological effects through its anti-inflammatory and anti-apoptotic properties in hepatotoxic, cancer and carcinogenic events. Whether this protective effect applies to ischemic injury in brain is still unknown, we therefore investigated the potential protective role of silibinin in ischemic stroke and the underlying mechanisms. Silibinin was administered intragastric 30 min before permanent middle cerebral artery occlusion (pMCAO). We found that silibinin significantly alleviated neurological deficit, reduced infarct volume, and suppressed brain edema, which were accompanied with upregulation of pAkt, pmTOR, HIF-1α, Bcl-2 and downregulation of Bax, NF-κB in ischemic brain tissue after stroke. Our results show that silibinin might exert anti-inflammatory and anti-apoptotic effects in ischemic brain through activating Akt/mTOR signaling.

Leonurine protects brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitochondria in experimental stroke

BACKGROUND It has been proved that pre-treatment with leonurine could protect brain tissue against ischemic injury by exerting antioxidant effects and regulating mitochondrial function. Whether this protective effect applies to acute phase after cerebral ischemia, we therefore investigate the potential neuroprotective role of leonurine and the underlying mechanisms in cerebral ischemia. METHODS Focal cerebral ischemia was induced in adult male Sprague-Dawley rats by permanent middle cerebral artery occlusion (MCAO). Leonurine was administered intraperitoneally at 7.5 or 15 mg/kg/d at 2h after surgery, then once daily thereafter. Neurological deficit, brain water content, and infarct volume were measured at 24h, 72 h, and 7d after stroke. Superoxide dismutase (SOD), catalase (CAT) activities, and malondialdehyde (MDA) content were also measured by spectrophotometer to evaluate oxidative reactions, and the expression of uncoupling protein 4 (UCP4), Bcl-2, and Bax were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical staining (IHC), and western blot, while the ultrastructure of the mitochondria were observed under transmission electron microscope. RESULTS Leonurine significantly alleviated neurological deficit, decreased brain water content and infarct volume after ischemic stroke, which was accompanied by decreased levels of MDA and Bax, increased activities of SOD, CAT, UCP4, and Bcl-2, and restored ultrastructure of mitochondria. CONCLUSIONS The results showed that leonurine protected brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitochondria in experimental stroke.

Parthenolide Is Neuroprotective in Rat Experimental Stroke Model: Downregulating NF-κB, Phospho-p38MAPK, and Caspase-1 and Ameliorating BBB Permeability

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Parthenolide (PN) has been proved to elicit a wide range of biological activities through its anti-inflammatory action in the treatment of migraine, arthritis, and atherosclerosis. To decide whether this effect applies to ischemic injury in brain, we therefore investigate the potential neuroprotective role of PN and the underlying mechanisms. Male Sprague-Dawley rats were randomly divided into Saline, Vehicle, and PN groups and a permanent middle cerebral artery occlusion (MCAO) model was used. PN administered intraperitoneally immediately after cerebral ischemia and once daily on the following days. At time points after MCAO, neurological deficit, infarct volume, and brain water content were measured. Immunohistochemistry, western blot and RT-PCR were used to analyze the expression of NF-κB and caspase-1 in ischemic brain tissue. Phospho-p38MAPK and claudin-5 were detected by western blot. The results indicated that PN dramatically ameliorated neurological deficit, brain water content, and infarct volume, downregulated NF-κB, phospho-p38MAPK, and caspase-1 expressions, and upregulated claudin-5 expression in ischemic brain tissue. Conclusions. PN protected the brain from damage caused by MCAO; this effect may be through downregulating NF-κB, phosho-p38MAPK, and caspase-1 expressions and ameliorating BBB permeability.

Protective effect of celastrol in rat cerebral ischemia model: down-regulating p-JNK, p-c-Jun and NF-κB.

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Celastrol has been proved to elicit a vanity of biological effects through its anti-oxidant, anti-inflammatory properties in the treatment of Alzheimers disease, systemic lupus erythematosus, and rheumatoid arthritis. However, little is known regarding the effect of celastrol in the acute phase of ischemic stroke. This study investigated the potential protective effects of celastrol and underlying mechanisms in cerebral ischemia. We used a permanent middle cerebral artery occlusion (pMCAO) model and administered celastrol intraperitoneally immediately after stroke. At 24h after stroke, we found that celastrol dramatically reduced neurological deficit, brain water content and infarct sizes, and downregulated the expression of p-JNK, p-c-Jun and NF-κB. The results indicated that celastrol may have the possibility of protective effect against ischemic injury, and this effect may be through downregulation of the expression of p-JNK, p-c-Jun and NF-κB.

Beneficial effects of sulindac in focal cerebral ischemia: A positive role in Wnt/β-catenin pathway

BACKGROUND Accumulated evidences have established that inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Sulindac is well known as a nonsteroidal anti-inflammatory drug. However, little is known regarding the effect of sulindac in acute cerebral ischemia. Here, we designed this study to investigate the potential protective effects of sulindac in focal cerebral ischemia and the mechanisms underlying in vivo. METHODS Focal cerebral ischemia was induced in male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Sulindac was administrated at dose of 4, 10, or 20mg/kg at 30 min before the operation. Neurological deficit scores, brain water content and infarct volumes were measured at 24h after pMCAO. Immunohistochemistry, western blot and reverse transcription-polymerase chain reaction were used for examining the mediators involved in Wnt/β-catenin signaling pathway, including the positive regulators dishevelled (Dvl) and β-catenin, the negative regulators adenomatous polyposis coli (APC), and P-β-catenin, as well as the downstream targets Bcl-2, Bax and claudin-5. RESULTS Compared with Vehicle group, 20mg/kg sulindac reduced neurological deficits, brain water content and infarct volumes. The same dose of sulindac upregulated the expression of Dvl, β-catenin, Bcl2 and claudin-5, and downregulated APC, P-β-catenin and Bax compared with Vehicle group. CONCLUSIONS These results showed that sulindac had a significant beneficial effect in cerebral ischemia; this effect may be correlated with the activation of the Wnt/β-catenin signaling.

Neuroprotective effect of early and short-time applying sophoridine in pMCAO rat brain: down-regulated TRAF6 and up-regulated p-ERK1/2 expression, ameliorated brain infaction and edema.

BACKGROUND Matrine has been proven to protect ischemic injury in brain and sophoridine (SOP) is an isomeride of matrine. It is unknown whether SOP has this protective effect on ischemic injury in brain. We therefore investigated the potential neuroprotective role of SOP and the underlying mechanism. METHODS Male, Sprague-Dawley rats were randomly assigned into five groups: Vehicle (pMCAO+saline), High dose (pMCAO+SOP 10 mg/kg), Middle dose (pMCAO+SOP 5 mg/kg), Low dose (pMCAO+SOP 2.5 mg/kg) and Sham operated group. Permanent middle cerebral artery occlusion (pMCAO) model was used and SOP was administered intraperitoneally immediately after cerebral ischemia and once daily in the following days. Neurological deficit was evaluated using a modified six point scale; brain water content and infarct volume were measured. The expression of TRAF6 and ERK1/2 were measured by immunohistochemistry, Western blotting. RESULTS Compared with Vehicle group, the cerebral edema was alleviated in High dose group (P<0.05), and the infarct volume was decreased in Low dose group (P<0.05). Consistent with these results, immunohistochemistry and Western blot analysis indicated that TRAF6 expression was significantly decreased in SOP administrated groups at 24 h, and the expression of phosphorylated ERK1/2 increased in Low dose at 72 h. CONCLUSIONS SOP protected the brain from damage caused by pMCAO, and this effect may be through down-regulation of TRAF6 expression and up-regulation of ERK1/2 phosphorylation expression.