Mechanism by which oleracein E alleviates TNBS-induced ulcerative colitis

Eur J Gastroenterol Hepatol. 2023 Aug 1;35(8):854-864. doi: 10.1097/MEG.0000000000002597. Epub 2023 Jun 15.

Abstract

Objective: This study aimed to investigate the effect of oleracein E (OE) in improving 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC).

Methods: Lipopolysaccharide (LPS) was used to induce a UC cell model, and TNBS was used to induce a UC rat model. ELISA was performed to assess the levels of inflammatory factors (IL-1β, TNF-α, and IL-6). Moreover, the activities of catalase (CAT), myeloperoxidase (MPO), and malonaldehyde (MDA) were detected by kits. Western blotting was performed to assess related proteins of the Nrf2/HO-1 signaling pathway, tight junction protein (ZO-1, Occludin, and claudin-2) expression levels, and apoptosis-related proteins (Bcl2, Bax, and cleaved caspase 3). Flow cytometry was used to analyze ROS levels. The morphology of colon tissues and the apoptosis of cells were detected by HE and TUNEL staining, respectively.

Results: OE significantly increased the activity of CAT and decreased the activity of MPO in LPS-induced Caco-2 cells and TNBS-induced UC rats. However, the levels of IL-1β, IL-6, and TNF-α were markedly reduced both in vivo and in vitro. In addition, OE significantly increased the levels of Nrf2/HO-1 signaling pathway-related proteins and tight junction proteins and inhibited cell apoptosis. HE staining showed that OE significantly decreased the severity of acute TNBS-induced colitis in rats.

Conclusion: OE may exert a regulatory effect on ameliorating intestinal barrier injury and reducing inflammation and oxidative stress levels by activating the Nrf2/HO-1 pathway.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Colitis*
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / metabolism
  • Humans
  • Interleukin-6
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • Rats
  • Trinitrobenzenesulfonic Acid / toxicity
  • Tumor Necrosis Factor-alpha

Substances

  • oleracein E
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Trinitrobenzenesulfonic Acid
  • Lipopolysaccharides
  • NF-E2-Related Factor 2