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Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice
Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a natura...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851626/ https://www.ncbi.nlm.nih.gov/pubmed/29538417 http://dx.doi.org/10.1371/journal.pone.0194069 |
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author | Yu, Xiu-Ting Xu, Yi-Fei Huang, Yan-Feng Qu, Chang Xu, Lie-Qiang Su, Zi-Ren Zeng, Hui-Fang Zheng, Lin Yi, Tie-Gang Li, Hui-Lin Chen, Jian-Ping Zhang, Xiao-Jun |
author_facet | Yu, Xiu-Ting Xu, Yi-Fei Huang, Yan-Feng Qu, Chang Xu, Lie-Qiang Su, Zi-Ren Zeng, Hui-Fang Zheng, Lin Yi, Tie-Gang Li, Hui-Lin Chen, Jian-Ping Zhang, Xiao-Jun |
author_sort | Yu, Xiu-Ting |
collection | PubMed |
description | Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC. |
format | Online Article Text |
id | pubmed-5851626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58516262018-03-23 Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice Yu, Xiu-Ting Xu, Yi-Fei Huang, Yan-Feng Qu, Chang Xu, Lie-Qiang Su, Zi-Ren Zeng, Hui-Fang Zheng, Lin Yi, Tie-Gang Li, Hui-Lin Chen, Jian-Ping Zhang, Xiao-Jun PLoS One Research Article Ulcerative colitis (UC) is a chronic relapsing disease without satisfactory treatments, in which intestinal inflammation and disrupted intestinal epithelial barrier are two main pathogeneses triggering UC. Berberrubine (BB) is deemed as one of the major active metabolite of berberine (BBR), a naturally-occurring isoquinoline alkaloid with appreciable anti-UC effect. This study aimed to comparatively investigate the therapeutic effects of BB and BBR on dextran sodium sulfate (DSS)-induced mouse colitis model, and explore the potential underlying mechanism. Results revealed that BB (20 mg/kg) produced a comparable therapeutic effect as BBR (50 mg/kg) and positive control sulfasalazine (200 mg/kg) by significantly reducing the disease activity index (DAI) with prolonged colon length and increased bodyweight as compared with the DSS group. BB treatment was shown to significantly ameliorate the DSS-induced colonic pathological alternations and decreased histological scores. In addition, BB markedly attenuated colonic inflammation by alleviating inflammatory cell infiltration and inhibiting myeloperoxidase (MPO) and cytokines (TNF-α, IFN-γ, IL-1β, IL-6, IL-4 and IL-10) productions in DSS mice. Furthermore, BB treatment substantially upregulated the expression of tight junction (TJ) proteins (zonula occludens-1, zonula occludens-2, claudin-1, occludin) and mRNA expression of mucins (mucin-1 and mucin-2), and decreased the Bax/Bcl-2 ratio. In summary, BB exerted similar effect to its analogue BBR and positive control in attenuating DSS-induced UC with much lower dosage and similar mechanism. The protective effect observed may be intimately associated with maintaining the integrity of the intestinal mucosal barrier and mitigating intestinal inflammation, which were mediated at least partially, via favorable modulation of TJ proteins and mucins and inhibition of inflammatory mediators productions in the colonic tissue. This is the first report to demonstrate that BB possesses pronounced anti-UC effect similar to BBR and sulfasalazine with much smaller dosage. BB might have the potential to be further developed into a promising therapeutic option in the treatment of UC. Public Library of Science 2018-03-14 /pmc/articles/PMC5851626/ /pubmed/29538417 http://dx.doi.org/10.1371/journal.pone.0194069 Text en © 2018 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Yu, Xiu-Ting Xu, Yi-Fei Huang, Yan-Feng Qu, Chang Xu, Lie-Qiang Su, Zi-Ren Zeng, Hui-Fang Zheng, Lin Yi, Tie-Gang Li, Hui-Lin Chen, Jian-Ping Zhang, Xiao-Jun Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice |
title | Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice |
title_full | Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice |
title_fullStr | Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice |
title_full_unstemmed | Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice |
title_short | Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice |
title_sort | berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5851626/ https://www.ncbi.nlm.nih.gov/pubmed/29538417 http://dx.doi.org/10.1371/journal.pone.0194069 |
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