Abstract

BACKGROUND: Intestinal epithelial barrier dysfunction is involved in the development and pathogenesis of intestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, and celiac disease. This study was performed to evaluate the ability of total flavonoid extract from hawthorn (TFH) to improve TNF-α-evoked intestinal epithelial barrier deficit.

MATERIAL AND METHODS: Caco-2 cells monolayers were exposed to TNF-α in different concentrations of TFH. Intestinal epithelial barrier function was evaluated using epithelial permeability and transepithelial electrical resistance (TER).

RESULTS: Our findings showed that TFH alleviated the increase of paracellular permeability and the decline of transepithelial electrical resistance (TER) evoked by TNF-α. Additionally, 24-h pre-incubation with TFH inhibited TNF-α-evoked secretion of pro-inflammatory factors (IL-6, IL-8, MCP-1, and IL-1β). Furthermore, TFH inhibited TNF-α-evoked overexpression of pMLC and MLCK and alleviated breakdown of TJs protein (ZO-1 and occludin). The activations of Elk-1 and NFκBp65 were inhibited by TFH pre-incubation.

CONCLUSIONS: TFH can alleviate TNF-α-evoked intestinal epithelial barrier deficit via the NFκBp65-mediated MLCK-MLC signaling pathway.

Keywords: Gastrointestinal Diseases, Tight Junction Proteins, Caco-2 Cells, Crataegus, Cytokines, Inflammation Mediators, Intestines, Myosin Light Chains, Myosin-Light-Chain Kinase, Phosphorylation, Plant Extracts, Protective Agents, Transcription Factor RelA, ets-Domain Protein Elk-1