Rhein protects against barrier disruption and inhibits inflammation in intestinal epithelial cells

Int Immunopharmacol. 2019 Jun:71:321-327. doi: 10.1016/j.intimp.2019.03.030. Epub 2019 Apr 2.

Abstract

Background and aims: Intestinal epithelial barrier and intestinal inflammation play indispensable roles in the development of intestinal diseases. The major aims of the current study were to investigate the potential of rhein, a major flavonoid compound isolated from Rheum rhabarbarum, in the treatment of intestinal diseases and its underlying mechanisms in vitro.

Methods: The protective role of rhein on intestinal epithelial barrier was evaluated in a monolayer of IEC-6 cells stimulated by TNF-α, while the anti-inflammatory effects were investigated in an IEC-6 cell model with LPS stimulation.

Results: Rhein inhibited the increase of phenol red flux and the decrease of TEER, as well as recovered the expression and distribution of ZO-1 and weakened MLC phosphorylation, MLCK expression and NF-κB activation. Meanwhile, LPS-stimulated IL-1β and IL-6 were down-regulated, expression levels of TLR4, NLRP3 and cleaved caspase1 were weakened and NF-κB was inactivated.

Conclusions: These results suggested that rhein has potential therapeutic effects against intestinal diseases by maintaining intestinal epithelial barrier and suppressing intestinal inflammation.

Keywords: Intestinal diseases; Intestinal epithelial barrier; Intestinal inflammation; Rhein.

MeSH terms

  • Animals
  • Anthraquinones / therapeutic use*
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Line
  • Inflammation / drug therapy*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Lipopolysaccharides / immunology
  • NF-kappa B / metabolism
  • Rats
  • Rheum / immunology
  • Signal Transduction
  • Tight Junctions / drug effects*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Anthraquinones
  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Tjp1 protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Zonula Occludens-1 Protein
  • rhein