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Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway

Growing evidences indicate that immune-mediated mechanisms contribute to the development of cerebral ischemia/reperfusion (I/R) injury. Daphnetin (DAP) is a coumarin derivative extracted from Daphne odora var., which displays anti-inflammatory properties. However, the effect of DAP on cerebral I/R i...

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Autores principales: Liu, Jia, Chen, Qianxue, Jian, Zhihong, Xiong, Xiaoxing, Shao, Lingmin, Jin, Tong, Zhu, Xiqun, Wang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227117/
https://www.ncbi.nlm.nih.gov/pubmed/28119924
http://dx.doi.org/10.1155/2016/2816056
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author Liu, Jia
Chen, Qianxue
Jian, Zhihong
Xiong, Xiaoxing
Shao, Lingmin
Jin, Tong
Zhu, Xiqun
Wang, Lei
author_facet Liu, Jia
Chen, Qianxue
Jian, Zhihong
Xiong, Xiaoxing
Shao, Lingmin
Jin, Tong
Zhu, Xiqun
Wang, Lei
author_sort Liu, Jia
collection PubMed
description Growing evidences indicate that immune-mediated mechanisms contribute to the development of cerebral ischemia/reperfusion (I/R) injury. Daphnetin (DAP) is a coumarin derivative extracted from Daphne odora var., which displays anti-inflammatory properties. However, the effect of DAP on cerebral I/R injury is not yet clear. Recent studies have demonstrated that TLR4/NF-κB signaling pathway takes part in the damaging inflammatory process of cerebral I/R injury. The present study aimed to investigate the effect of DAP on cerebral I/R injury in vivo and its possible mechanisms. DAP was administered before middle cerebral artery occlusion and reperfusion in mice. The neurological scores, cerebral infarct sizes, the levels of inflammatory cytokines, apoptotic neural cells, and the levels of TLR4, NF-κB p65, and IκBα were estimated. The results showed that an obvious improvement of neurological scores and infarct sizes was observed in DAP-treated mice after MCAO/R. DAP treatment decreased the overexpression of TNF-α, IL-1β, and IL-6 and attenuated neural cells apoptosis. Moreover, DAP treatment decreased the TLR4 expression, IκB-α degradation, and nuclear translocation of NF-κB. Taken together, our results suggested that DAP exerted neuroprotective and anti-inflammatory effects on cerebral I/R injury. The potential mechanism was involved in the inhibition of TLR4/NF-κB mediated inflammatory signaling pathway.
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spelling pubmed-52271172017-01-24 Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway Liu, Jia Chen, Qianxue Jian, Zhihong Xiong, Xiaoxing Shao, Lingmin Jin, Tong Zhu, Xiqun Wang, Lei Biomed Res Int Research Article Growing evidences indicate that immune-mediated mechanisms contribute to the development of cerebral ischemia/reperfusion (I/R) injury. Daphnetin (DAP) is a coumarin derivative extracted from Daphne odora var., which displays anti-inflammatory properties. However, the effect of DAP on cerebral I/R injury is not yet clear. Recent studies have demonstrated that TLR4/NF-κB signaling pathway takes part in the damaging inflammatory process of cerebral I/R injury. The present study aimed to investigate the effect of DAP on cerebral I/R injury in vivo and its possible mechanisms. DAP was administered before middle cerebral artery occlusion and reperfusion in mice. The neurological scores, cerebral infarct sizes, the levels of inflammatory cytokines, apoptotic neural cells, and the levels of TLR4, NF-κB p65, and IκBα were estimated. The results showed that an obvious improvement of neurological scores and infarct sizes was observed in DAP-treated mice after MCAO/R. DAP treatment decreased the overexpression of TNF-α, IL-1β, and IL-6 and attenuated neural cells apoptosis. Moreover, DAP treatment decreased the TLR4 expression, IκB-α degradation, and nuclear translocation of NF-κB. Taken together, our results suggested that DAP exerted neuroprotective and anti-inflammatory effects on cerebral I/R injury. The potential mechanism was involved in the inhibition of TLR4/NF-κB mediated inflammatory signaling pathway. Hindawi Publishing Corporation 2016 2016-12-29 /pmc/articles/PMC5227117/ /pubmed/28119924 http://dx.doi.org/10.1155/2016/2816056 Text en
spellingShingle Research Article
Liu, Jia
Chen, Qianxue
Jian, Zhihong
Xiong, Xiaoxing
Shao, Lingmin
Jin, Tong
Zhu, Xiqun
Wang, Lei
Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway
title Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway
title_full Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway
title_fullStr Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway
title_full_unstemmed Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway
title_short Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-κB Signaling Pathway
title_sort daphnetin protects against cerebral ischemia/reperfusion injury in mice via inhibition of tlr4/nf-κb signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227117/
https://www.ncbi.nlm.nih.gov/pubmed/28119924
http://dx.doi.org/10.1155/2016/2816056
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