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Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke

BACKGROUND: Ischemic brain injury is associated with neuroinflammatory response, which essentially involves glial activation and neutrophil infiltration. Transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) contribute to ischemic neuroinflamm...

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Autores principales: Yu, Lu, Chen, Chu, Wang, Liang-Fen, Kuang, Xi, Liu, Ke, Zhang, Hao, Du, Jun-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577792/
https://www.ncbi.nlm.nih.gov/pubmed/23437066
http://dx.doi.org/10.1371/journal.pone.0055839
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author Yu, Lu
Chen, Chu
Wang, Liang-Fen
Kuang, Xi
Liu, Ke
Zhang, Hao
Du, Jun-Rong
author_facet Yu, Lu
Chen, Chu
Wang, Liang-Fen
Kuang, Xi
Liu, Ke
Zhang, Hao
Du, Jun-Rong
author_sort Yu, Lu
collection PubMed
description BACKGROUND: Ischemic brain injury is associated with neuroinflammatory response, which essentially involves glial activation and neutrophil infiltration. Transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) contribute to ischemic neuroinflammatory processes and secondary brain injury by releasing proinflammatory mediators. Kaempferol-3-O-rutinoside (KRS) and kaempferol-3-O- glucoside (KGS) are primary flavonoids found in Carthamus tinctorius L. Recent studies demonstrated that KRS protected against ischemic brain injury. However, little is known about the underlying mechanisms. Flavonoids have been reported to have antiinflammatory properties. Herein, we explored the effects of KRS and KGS in a transient focal stroke model. METHODOLOGY/PRINCIPAL FINDINGS: Rats were subjected to middle cerebral artery occlusion for 2 hours followed by 22 h reperfusion. An equimolar dose of KRS or KGS was administered i.v. at the beginning of reperfusion. The results showed that KRS or KGS significantly attenuated the neurological deficits, brain infarct volume, and neuron and axon injury, reflected by the upregulation of neuronal nuclear antigen-positive neurons and downregulation of amyloid precursor protein immunoreactivity in the ipsilateral ischemic hemisphere. Moreover, KRS and KGS inhibited the expression of OX-42, glial fibrillary acidic protein, phosphorylated STAT3 and NF-κB p65, and the nuclear content of NF-κB p65. Subsequently, these flavonoids inhibited the expression of tumor necrosis factor α, interleukin 1β, intercellular adhesion molecule 1, matrix metallopeptidase 9, inducible nitric oxide synthase, and myeloperoxidase. CONCLUSION/SIGNIFICANCE: Our findings suggest that postischemic treatment with KRS or KGS prevents ischemic brain injury and neuroinflammation by inhibition of STAT3 and NF-κB activation and has the therapeutic potential for the neuroinflammation-related diseases, such as ischemic stroke.
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spelling pubmed-35777922013-02-22 Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke Yu, Lu Chen, Chu Wang, Liang-Fen Kuang, Xi Liu, Ke Zhang, Hao Du, Jun-Rong PLoS One Research Article BACKGROUND: Ischemic brain injury is associated with neuroinflammatory response, which essentially involves glial activation and neutrophil infiltration. Transcription factors nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) contribute to ischemic neuroinflammatory processes and secondary brain injury by releasing proinflammatory mediators. Kaempferol-3-O-rutinoside (KRS) and kaempferol-3-O- glucoside (KGS) are primary flavonoids found in Carthamus tinctorius L. Recent studies demonstrated that KRS protected against ischemic brain injury. However, little is known about the underlying mechanisms. Flavonoids have been reported to have antiinflammatory properties. Herein, we explored the effects of KRS and KGS in a transient focal stroke model. METHODOLOGY/PRINCIPAL FINDINGS: Rats were subjected to middle cerebral artery occlusion for 2 hours followed by 22 h reperfusion. An equimolar dose of KRS or KGS was administered i.v. at the beginning of reperfusion. The results showed that KRS or KGS significantly attenuated the neurological deficits, brain infarct volume, and neuron and axon injury, reflected by the upregulation of neuronal nuclear antigen-positive neurons and downregulation of amyloid precursor protein immunoreactivity in the ipsilateral ischemic hemisphere. Moreover, KRS and KGS inhibited the expression of OX-42, glial fibrillary acidic protein, phosphorylated STAT3 and NF-κB p65, and the nuclear content of NF-κB p65. Subsequently, these flavonoids inhibited the expression of tumor necrosis factor α, interleukin 1β, intercellular adhesion molecule 1, matrix metallopeptidase 9, inducible nitric oxide synthase, and myeloperoxidase. CONCLUSION/SIGNIFICANCE: Our findings suggest that postischemic treatment with KRS or KGS prevents ischemic brain injury and neuroinflammation by inhibition of STAT3 and NF-κB activation and has the therapeutic potential for the neuroinflammation-related diseases, such as ischemic stroke. Public Library of Science 2013-02-20 /pmc/articles/PMC3577792/ /pubmed/23437066 http://dx.doi.org/10.1371/journal.pone.0055839 Text en © 2013 Yu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yu, Lu
Chen, Chu
Wang, Liang-Fen
Kuang, Xi
Liu, Ke
Zhang, Hao
Du, Jun-Rong
Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke
title Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke
title_full Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke
title_fullStr Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke
title_full_unstemmed Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke
title_short Neuroprotective Effect of Kaempferol Glycosides against Brain Injury and Neuroinflammation by Inhibiting the Activation of NF-κB and STAT3 in Transient Focal Stroke
title_sort neuroprotective effect of kaempferol glycosides against brain injury and neuroinflammation by inhibiting the activation of nf-κb and stat3 in transient focal stroke
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577792/
https://www.ncbi.nlm.nih.gov/pubmed/23437066
http://dx.doi.org/10.1371/journal.pone.0055839
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