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

Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
Brain research (Impact Factor: 2.84). 05/2012; 1464:8-13. DOI: 10.1016/j.brainres.2012.04.054
Source: PubMed


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 Alzheimer's 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.

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    • "Furthermore, ectopic expression of dn-c-Jun also strengthened celastrol inhibition of Cd-induced neuronal apoptosis. Our finding is in consistence with a recent report that celastrol has protective effect in rat cerebral ischemia model through down-regulation of phospho-JNK and phospho-c- Jun (Li et al. 2012). Therefore, our data support the notion that celastrol protects against Cd-induced neuronal apoptosis partially by blocking JNK pathway. "
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