1. Academic Validation
  2. Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice

  • PLoS One. 2018 Mar 14;13(3):e0194069. doi: 10.1371/journal.pone.0194069.
Xiu-Ting Yu 1 Yi-Fei Xu 2 Yan-Feng Huang 3 Chang Qu 3 Lie-Qiang Xu 3 Zi-Ren Su 3 4 Hui-Fang Zeng 1 Lin Zheng 5 Tie-Gang Yi 5 Hui-Lin Li 5 Jian-Ping Chen 5 Xiao-Jun Zhang 2
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China.
  • 2 School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China.
  • 3 Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China.
  • 4 Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, Guangdong, PR China.
  • 5 Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, PR China.
Abstract

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.

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