Department of General Anorectal Surgery, Jingjiang People's Hospital, Jingjiang, Jiangsu, China (mainland).
Central Laboratory, Jingjiang People's Hospital, Jingjiang, Jiangsu, China (mainland).
Med Sci Monit. 2020 Feb 17;26:e920170. doi: 10.12659/MSM.920170.
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-alpha-evoked intestinal epithelial barrier deficit. MATERIAL AND METHODS Caco-2 cells monolayers were exposed to TNF-alpha 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-alpha. Additionally, 24-h pre-incubation with TFH inhibited TNF-alpha-evoked secretion of pro-inflammatory factors (IL-6, IL-8, MCP-1, and IL-1ß). Furthermore, TFH inhibited TNF-alpha-evoked overexpression of pMLC and MLCK and alleviated breakdown of TJs protein (ZO-1 and occludin). The activations of Elk-1 and NFkappaBp65 were inhibited by TFH pre-incubation. CONCLUSIONS TFH can alleviate TNF-alpha-evoked intestinal epithelial barrier deficit via the NFkappaBp65-mediated MLCK-MLC signaling pathway.
肠道上皮屏障功能障碍与肠道疾病（如肠易激综合征、炎症性肠病和乳糜泻）的发生和发病机制有关。本研究旨在评估山楂总黄酮提取物（TFH）改善 TNF-α 诱导的肠道上皮屏障缺陷的能力。
将 Caco-2 细胞单层暴露于不同浓度的 TFH 中的 TNF-α。通过上皮通透性和跨上皮电阻（TER）评估肠道上皮屏障功能。
我们的研究结果表明，TFH 减轻了 TNF-α 诱导的旁通透性增加和跨上皮电阻（TER）下降。此外，TFH 抑制了 TNF-α 诱导的促炎因子（IL-6、IL-8、MCP-1 和 IL-1β）的分泌。此外，TFH 抑制了 TNF-α 诱导的 TJ 蛋白（ZO-1 和 occludin）的过度表达和 MLCK 的磷酸化。TFH 预处理抑制了 Elk-1 和 NFκBp65 的激活。
TFH 可以通过 NFκBp65 介导的 MLCK-MLC 信号通路减轻 TNF-α 诱导的肠道上皮屏障缺陷。
