Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway

Int Immunopharmacol. 2019 Oct:75:105768. doi: 10.1016/j.intimp.2019.105768. Epub 2019 Aug 2.

Abstract

Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) which has become a global public health problem. Limonin is a triterpenoid extracted from citrus which possesses the capacities to against inflammations and cell apoptosis. However, the efficacy and the underlying mechanisms of limonin in the treatment of UC remain unclear. In this study, we first investigated the therapeutic effects of limonin on dextran sodiumsulfate (DSS)-induced UC in vivo by examining the changes of disease activity index (DAI), the colon length, the colon histology, and cyto/chemokine levels. We found that limonin markedly reduced DAI, intestinal damages, and the levels of pro-inflammatory cytokines, such as TNF-α and IL-6. In vitro, limonin significantly repressed the productions of pro-inflammatory cytokines in cultured normal colonic epithelial cells. Mechanistically, we demonstrated that limonin improved the prognosis of UC mainly through downregulating p-STAT3/miR-214 levels. Collectively, our results suggested that limonin was a novel therapeutic agent and it was expected to be translated into the clinic to improve the prognosis of UC.

Keywords: DSS; Limonin; PTEN; Ulcerative colitis; miR-214; p-STAT3.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Line
  • Cell Survival / drug effects
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology
  • Colon / drug effects
  • Colon / immunology
  • Colon / pathology
  • Dextran Sulfate
  • Epithelial Cells / drug effects
  • Interleukin-10 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Limonins / pharmacology
  • Limonins / therapeutic use*
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / immunology*
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • IL10 protein, mouse
  • Interleukin-6
  • Limonins
  • MicroRNAs
  • Mirn214 microRNA, mouse
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • interleukin-6, mouse
  • Interleukin-10
  • Dextran Sulfate
  • limonin