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Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia

The gut-brain interaction is associated with impaired duodenal mucosal integrity and low-grade inflammation, which have been proven to be important pathological mechanisms of functional dyspepsia (FD). Sini San (SNS) is a classical Chinese medicine used to treat FD, but its underlying mechanisms are...

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Autores principales: Zhu, Chunyang, Zhao, Luqing, Zhao, Jingyi, Zhang, Shengsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889936/
https://www.ncbi.nlm.nih.gov/pubmed/31746413
http://dx.doi.org/10.3892/ijmm.2019.4394
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author Zhu, Chunyang
Zhao, Luqing
Zhao, Jingyi
Zhang, Shengsheng
author_facet Zhu, Chunyang
Zhao, Luqing
Zhao, Jingyi
Zhang, Shengsheng
author_sort Zhu, Chunyang
collection PubMed
description The gut-brain interaction is associated with impaired duodenal mucosal integrity and low-grade inflammation, which have been proven to be important pathological mechanisms of functional dyspepsia (FD). Sini San (SNS) is a classical Chinese medicine used to treat FD, but its underlying mechanisms are poorly understood. The aim of the present study was to evaluate the effects of SNS on duodenal mucosal barrier injury and low-grade inflammation with FD, and to assess its potential molecular mechanisms on the brain-gut axis. FD rats were established using the iodoacetamide and tail-squeezed methods. The expression of corticotropin-releasing factor (CRF), CRF receptor 1 (CRF-R1) and CRF-R2, were determined by western blot analysis and/or immunohistochemistry (IHC). In addition, mast cell (MC) migration was assessed by IHC with an anti-tryptase antibody, and histamine concentration was quantified using ELISA. The mRNA expression levels of tryptase and protease-activated receptor 2 (PAR-2) were quantified using reverse transcription-quantitative PCR, and the protein expression levels of zona occludens protein 1 (ZO-1), junctional adhesion molecule 1 (JAM-1), β-catenin and E-cadherin were determined via western blot analysis. It was demonstrated that the expression level of CRF was downregulated in the central nervous system and duodenum following SNS treatment, and that SNS modulated the expression of both CRF-R1 and CRF-R2. In addition, SNS suppressed MC infiltration and the activity of the tryptase/PAR-2 pathway in the duodenum. Furthermore, treatment with SNS restored the normal expression levels of ZO-1, JAM-1 and β-catenin in FD rats. These findings suggested that the therapeutic effects of SNS on FD were achieved by restoring mucosal barrier integrity and suppressing low-grade inflammation in the duodenum, which was at least partially mediated via the CRF signaling pathway.
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spelling pubmed-68899362019-12-06 Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia Zhu, Chunyang Zhao, Luqing Zhao, Jingyi Zhang, Shengsheng Int J Mol Med Articles The gut-brain interaction is associated with impaired duodenal mucosal integrity and low-grade inflammation, which have been proven to be important pathological mechanisms of functional dyspepsia (FD). Sini San (SNS) is a classical Chinese medicine used to treat FD, but its underlying mechanisms are poorly understood. The aim of the present study was to evaluate the effects of SNS on duodenal mucosal barrier injury and low-grade inflammation with FD, and to assess its potential molecular mechanisms on the brain-gut axis. FD rats were established using the iodoacetamide and tail-squeezed methods. The expression of corticotropin-releasing factor (CRF), CRF receptor 1 (CRF-R1) and CRF-R2, were determined by western blot analysis and/or immunohistochemistry (IHC). In addition, mast cell (MC) migration was assessed by IHC with an anti-tryptase antibody, and histamine concentration was quantified using ELISA. The mRNA expression levels of tryptase and protease-activated receptor 2 (PAR-2) were quantified using reverse transcription-quantitative PCR, and the protein expression levels of zona occludens protein 1 (ZO-1), junctional adhesion molecule 1 (JAM-1), β-catenin and E-cadherin were determined via western blot analysis. It was demonstrated that the expression level of CRF was downregulated in the central nervous system and duodenum following SNS treatment, and that SNS modulated the expression of both CRF-R1 and CRF-R2. In addition, SNS suppressed MC infiltration and the activity of the tryptase/PAR-2 pathway in the duodenum. Furthermore, treatment with SNS restored the normal expression levels of ZO-1, JAM-1 and β-catenin in FD rats. These findings suggested that the therapeutic effects of SNS on FD were achieved by restoring mucosal barrier integrity and suppressing low-grade inflammation in the duodenum, which was at least partially mediated via the CRF signaling pathway. D.A. Spandidos 2020-01 2019-11-04 /pmc/articles/PMC6889936/ /pubmed/31746413 http://dx.doi.org/10.3892/ijmm.2019.4394 Text en Copyright: © Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Zhu, Chunyang
Zhao, Luqing
Zhao, Jingyi
Zhang, Shengsheng
Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia
title Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia
title_full Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia
title_fullStr Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia
title_full_unstemmed Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia
title_short Sini San ameliorates duodenal mucosal barrier injury and low-grade inflammation via the CRF pathway in a rat model of functional dyspepsia
title_sort sini san ameliorates duodenal mucosal barrier injury and low-grade inflammation via the crf pathway in a rat model of functional dyspepsia
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889936/
https://www.ncbi.nlm.nih.gov/pubmed/31746413
http://dx.doi.org/10.3892/ijmm.2019.4394
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