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

Lǐ, Yànhuá; He, Dan; Zhang, Xiangjian; Liu, Zongjie; Zhang, Xiaolin; Dong, Lipeng; Xing, Yinxue; Wang, ChaoHui; Qiao, Huimin; Zhu, Changlian; Chen, Yulin

doi:10.1016/j.brainres.2012.04.054

Cited by 73 publications

(64 citation statements)

References 37 publications

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“…Celastrol has been shown to be protective against cerebral ischemia, Alzheimer's disease, and SLE as well as rheumatoid arthritis (Li et al . ). The triterpenoid Celastrol and other specific structural analogues were originally discovered through screen for drugs to treat amyotrophic artheroscelerosis and Huntington's disease (Westerheide et al .…”

Section: Discussionmentioning

confidence: 97%

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Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury

Eroglu

Kimbler

Pang

et al. 2014

Journal of Neurochemistry

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Traumatic brain injury (TBI) induces severe harm and disability in many accident victims and combat-related activities. The heat shock proteins Hsp70/Hsp110 protect cells against death and ischemic damage. In this study, we used mice deficient in Hsp110 or Hsp70 to examine their potential requirement following TBI. Data indicate that loss of Hsp110 or Hsp70 increases brain injury and death of neurons. One of the mechanisms underlying the increased cell death observed in the absence of Hsp110 and Hsp70 following TBI is the increased expression of ROS-induced p53 target genes Pig1, Pig8 and Pig12. To examine whether drugs that increase the levels of Hsp70/Hsp110 can protect cells against TBI, we subjected mice to TBI and administered Celastrol or BGP-15. In contrast to Hsp110 or Hsp70i-deficient mice that were not protected following TBI and Celastrol treatment, there was a significant improvement of wild-type mice following administration of these drugs during the first week following TBI. In addition, assessment of neurological injury shows significant improvement of Contextual and Cued Fear Conditioning tests and beam balance in wild-type mice that were treated with Celastrol or BGP-15 following TBI compared to TBI-treated mice. These studies indicate a significant role of Hsp70/Hsp110 in neuronal survival following TBI and the beneficial effects of Hsp70/Hsp110 inducers toward reducing the pathological consequences of TBI.

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Section: Discussionmentioning

confidence: 97%

“…For the in vivo drug treatments, mice were treated with 1 mg/kg of Celastrol (Li et al . ) at 30 min and 6 h, and then again once daily for 5 days post‐TBI given intraperitoneally. O‐(3‐piperidino‐2‐hydroxy‐1‐propyl)nicotinic amidoxime (BGP‐15) was administered orally at 15 mg/kg (Gehrig et al .…”

Section: Methodsmentioning

confidence: 99%

Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury

Eroglu

Kimbler

Pang

et al. 2014

Journal of Neurochemistry

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“…The infarct volume was assessed using the 2,3,5-triphenyltetrazolium chloride (TTC) method, as described previously (16). The rats were sacrificed and the brains were extracted following the measurement of the neurological deficit score.…”

Section: Methodsmentioning

confidence: 99%

Protective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins, isolated from Pana quinquefolium, on permanent focal cerebral ischemic injury in rats

et al. 2013

Experimental and Therapeutic Medicine

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Oxidative stress is significant in the pathogenesis of cerebral ischemia. Panax quinquefolium 20(S)-protopanaxadiol saponins (PQDS) have been demonstrated to exhibit a variety of biological effects in the cardiovascular system as a result of their antioxidant properties. However, little is known regarding the effect of PQDS on cerebral ischemia. The purpose of this study was to investigate whether PQDS exhibited protective effects against cerebral ischemia. A model of cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in Sprague-Dawley rats. Adult male rats were randomly divided into five groups: Sham, MCAO and PQDS treatment groups at doses of 12.5, 25.0 and 50.0 mg/kg. The effects of PQDS on neurological deficits, cerebral infarct area, brain water content, and the malondialdehyde (MDA) and Ca2+ levels and Na+-K+-ATPase and superoxide dismutase (SOD) activities in the brain tissue were analyzed, and the nitric oxide (NO) content and nitric oxide synthase (NOS) activity in the serum were evaluated. Moreover, the expression of Bcl-2 was analyzed using western blotting. Pretreatment with PQDS (25.0 and 50.0 mg/kg) significantly reduced the neurological deficit score, decreased the infarcted area and decreased the brain water content from 83.09 to 80.27% (P<0.05). In addition, PQDS pretreatment decreased the NOS activity and the NO levels in the serum compared with those in the MCAO group. Furthermore, pretreatment with PQDS (25.0 and 50.0 mg/kg) significantly increased the activities of SOD and Na+-K+-ATPase and decreased the levels of Ca2+ and MDA in the brain tissue (P<0.05) compared with those in the MCAO group. Pretreatment with PQDS (25.0 and 50.0 mg/kg) also increased the protein expression level of Bcl-2 compared with that in the MCAO group. The histopathological results demonstrated the protective effect of PQDS on ischemic injury. The results indicated that PQDS has protective effects against ischemic injury in rats. The mechanism may be associated with the inhibition of oxidative stress and apoptosis.

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“…Many trials are ongoing for the treatment of many diseases, such as RA, by inhibiting NF-kB (Kannaiyan et al, 2011a(Kannaiyan et al, , 2011bLi et al, 2012). Many trials are ongoing for the treatment of many diseases, such as RA, by inhibiting NF-kB (Kannaiyan et al, 2011a(Kannaiyan et al, , 2011bLi et al, 2012).…”

Section: Differences In Results and Conclusion In Comparison With Othmentioning

confidence: 99%

Nuclear factor-κB and basic fibroblast growth factor augment pannus formation in rheumatoid synovitis

Ibrahim¹,

Salman²,

Ibrahim³

et al. 2013

Egyptian Journal of Pathology

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

Cited by 73 publications

References 37 publications

Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury

Therapeutic inducers of the HSP70/HSP110 protect mice against traumatic brain injury

Protective effect of Panax quinquefolium 20(S)-protopanaxadiol saponins, isolated from Pana quinquefolium, on permanent focal cerebral ischemic injury in rats

Nuclear factor-κB and basic fibroblast growth factor augment pannus formation in rheumatoid synovitis

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