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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5851626?pdf=render |
| _version_ | 1819170216270102528 |
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| author | Xiu-Ting Yu Yi-Fei Xu Yan-Feng Huang Chang Qu Lie-Qiang Xu Zi-Ren Su Hui-Fang Zeng Lin Zheng Tie-Gang Yi Hui-Lin Li Jian-Ping Chen Xiao-Jun Zhang |
| author_facet | Xiu-Ting Yu Yi-Fei Xu Yan-Feng Huang Chang Qu Lie-Qiang Xu Zi-Ren Su Hui-Fang Zeng Lin Zheng Tie-Gang Yi Hui-Lin Li Jian-Ping Chen Xiao-Jun Zhang |
| author_sort | Xiu-Ting Yu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T19:31:52Z |
| format | Article |
| id | doaj.art-d70bc3acec404128aeff8e3ba8715711 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T19:31:52Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d70bc3acec404128aeff8e3ba87157112022-12-21T18:15:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01133e019406910.1371/journal.pone.0194069Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice.Xiu-Ting YuYi-Fei XuYan-Feng HuangChang QuLie-Qiang XuZi-Ren SuHui-Fang ZengLin ZhengTie-Gang YiHui-Lin LiJian-Ping ChenXiao-Jun ZhangUlcerative 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.http://europepmc.org/articles/PMC5851626?pdf=render |
| spellingShingle | Xiu-Ting Yu Yi-Fei Xu Yan-Feng Huang Chang Qu Lie-Qiang Xu Zi-Ren Su Hui-Fang Zeng Lin Zheng Tie-Gang Yi Hui-Lin Li Jian-Ping Chen Xiao-Jun Zhang Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC5851626?pdf=render |
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