Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Yu-Chen, Li, Yi, Zhang, Yu-Ning, Zhao, Qiong, Zhang, Pei-Lin, Sun, Meng-Ru, Liu, Bao-Lin, Yang, Hua, Li, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784771448775114752
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
work_keys_str_mv AT liyuchen musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT liyi musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT zhangyuning musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT zhaoqiong musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT zhangpeilin musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT sunmengru musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT liubaolin musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT yanghua musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury
AT liping musconeandborneolcooperativelystrengthencrebinductionofclaudin5inil1binducedendotheliuminjury