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Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury
Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether mu...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394259/ https://www.ncbi.nlm.nih.gov/pubmed/35892657 http://dx.doi.org/10.3390/antiox11081455 |
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author | Li, Yu-Chen Li, Yi Zhang, Yu-Ning Zhao, Qiong Zhang, Pei-Lin Sun, Meng-Ru Liu, Bao-Lin Yang, Hua Li, Ping |
author_facet | Li, Yu-Chen Li, Yi Zhang, Yu-Ning Zhao, Qiong Zhang, Pei-Lin Sun, Meng-Ru Liu, Bao-Lin Yang, Hua Li, Ping |
author_sort | Li, Yu-Chen |
collection | PubMed |
description | Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and (+)-borneol combination protected claudin 5 by targeting ROS-mediated IL-1β accumulation. Muscone and (+)-borneol reduced cerebral infarct volume and cerebrovascular leakage with claudin 5 protection in mice after stroke, largely due to inhibiting ROS accumulation and inflammatory infiltrate of microglia. Muscone reduced ROS and then blocked the CaN/Erk1/2 pathway to decrease IL-1β release, while (+)-borneol removed mitochondrial ROS and attenuated the SDH/Hif-1α pathway to inhibit IL-1β transcription, thereby jointly reducing IL-1β production. Accumulated IL-1β disrupted cAMP/CREB activation and attenuated transcriptional regulation of claudin 5. Muscone and (+)-borneol combination cooperatively protected BBB function by blocking IL-1β-mediated cAMP/CREB/claudin 5 cascades. Mutation of Ser133 site of CREB or knockdown of claudin 5 weakened the effects of muscone and (+)-borneol on upregulation of TEER value and downregulation of FITC-dextran permeability, suggesting that targeting CREB/claudin 5 was an important strategy to protect vascular integrity. This study provided ideas for the studies of synergistic protection against ischemic brain injury about the active ingredients of traditional Chinese medicines (TCMs). |
format | Online Article Text |
id | pubmed-9394259 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93942592022-08-23 Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury Li, Yu-Chen Li, Yi Zhang, Yu-Ning Zhao, Qiong Zhang, Pei-Lin Sun, Meng-Ru Liu, Bao-Lin Yang, Hua Li, Ping Antioxidants (Basel) Article Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and (+)-borneol combination protected claudin 5 by targeting ROS-mediated IL-1β accumulation. Muscone and (+)-borneol reduced cerebral infarct volume and cerebrovascular leakage with claudin 5 protection in mice after stroke, largely due to inhibiting ROS accumulation and inflammatory infiltrate of microglia. Muscone reduced ROS and then blocked the CaN/Erk1/2 pathway to decrease IL-1β release, while (+)-borneol removed mitochondrial ROS and attenuated the SDH/Hif-1α pathway to inhibit IL-1β transcription, thereby jointly reducing IL-1β production. Accumulated IL-1β disrupted cAMP/CREB activation and attenuated transcriptional regulation of claudin 5. Muscone and (+)-borneol combination cooperatively protected BBB function by blocking IL-1β-mediated cAMP/CREB/claudin 5 cascades. Mutation of Ser133 site of CREB or knockdown of claudin 5 weakened the effects of muscone and (+)-borneol on upregulation of TEER value and downregulation of FITC-dextran permeability, suggesting that targeting CREB/claudin 5 was an important strategy to protect vascular integrity. This study provided ideas for the studies of synergistic protection against ischemic brain injury about the active ingredients of traditional Chinese medicines (TCMs). MDPI 2022-07-26 /pmc/articles/PMC9394259/ /pubmed/35892657 http://dx.doi.org/10.3390/antiox11081455 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Yu-Chen Li, Yi Zhang, Yu-Ning Zhao, Qiong Zhang, Pei-Lin Sun, Meng-Ru Liu, Bao-Lin Yang, Hua Li, Ping Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury |
title | Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury |
title_full | Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury |
title_fullStr | Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury |
title_full_unstemmed | Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury |
title_short | Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury |
title_sort | muscone and (+)-borneol cooperatively strengthen creb induction of claudin 5 in il-1β-induced endothelium injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9394259/ https://www.ncbi.nlm.nih.gov/pubmed/35892657 http://dx.doi.org/10.3390/antiox11081455 |
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