Protective effects of iridoid glycosides on acute colitis via inhibition of the inflammatory response mediated by the STAT3/NF-кB pathway

Int Immunopharmacol. 2020 Apr:81:106240. doi: 10.1016/j.intimp.2020.106240. Epub 2020 Feb 7.

Abstract

Morroniside and loganin are iridoid glycosides extracted from Cornus officinalis, a plant species widely used in traditional Chinese medicine. However, the anti-inflammatory effects of morroniside and loganin in colitis are barely understood. The aim of the present study was to explore the effects of morroniside and loganin on the dextran sodium sulfate (DSS)-induced murine model of colitis and an LPS-induced colorectal cancer (CRC) cell inflammation model, and to clarify the underlying mechanisms. We found that morroniside and loganin were able to ameliorate clinical features, including disease activity index (DAI), histological inflammation score and periodic acid-Schiff staining (PAS). In the mouse model, morroniside and loganin treatment increased expression of tight junction proteins (TJs) and decreased pro-inflammatory cytokine production. Moreover, our findings showed that the expression of p-STAT3 and p-p65 were suppressed compared to the disease group. In in vitro experiments, treatment with morroniside and loganin had no obvious effects on proliferative activity in HCT116 cells and HIEC-6 cells. Expression of pro-inflammatory cytokines was inhibited by morroniside and loganin treatment in comparison with the LPS-treated group. Taken together, morroniside and loganin have beneficial effects on colitis in vivo and are anti-inflammatory in vitro. Possible mechanisms of the anti-inflammatory response may include blockade of the STAT3/NF-κB pathway.

Keywords: Colitis; Inflammatory response; Iridoid glycosides; STAT3/NF-кB.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Line
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis, Ulcerative / drug therapy*
  • Cornus / immunology
  • Dextran Sulfate
  • Disease Models, Animal
  • Glycosides / therapeutic use*
  • Humans
  • Iridoid Glycosides / therapeutic use*
  • Iridoids / therapeutic use*
  • Male
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Phosphorylation
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Glycosides
  • Iridoid Glycosides
  • Iridoids
  • NF-kappa B
  • STAT3 Transcription Factor
  • morroniside
  • Dextran Sulfate
  • loganin