College of Food Science, Northeast Agricultural University, Harbin 150030, China.
College of Food Science, Northeast Agricultural University, Harbin 150030, China; Heilongjiang Green Food Science Research Institute, Northeast Agricultural University, Harbin 150030, China.
Food Res Int. 2022 Aug;158:111502. doi: 10.1016/j.foodres.2022.111502. Epub 2022 Jun 13.
Intestinal epithelial barrier dysfunction can cause several intestinal diseases. Flavonoids have been shown to be beneficial to the intestinal epithelial barrier function. However, the effects of taxifolin (TAX), a naturally occurring flavonoid, on the intestinal epithelial barrier function are unclear. Thus, the aims of this study were to investigate the protective effect and potential mechanism of TAX against lipopolysaccharide (LPS)-induced intestinal epithelial barrier dysfunction in a Caco-2 cell monolayer model. Our results showed that TAX increased the transepithelial electrical resistance (TEER) and decreased the fluorescein isothiocyanate (FITC)-dextran (4 kDa) flux in the damaged intestinal epithelial barrier. Meanwhile, TAX inhibited an LPS-induced decrease in mRNA and protein expression of tight junction (TJ) proteins (claudin-1, zonula occludens [ZO]-1, and occludin), and ameliorating the continuous distribution pattern disrupted of TJs. These results suggested that TAX ameliorated intestinal epithelial barrier dysfunction. Regarding the underlying mechanism, TAX reduced the LPS-induced secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in Caco-2 cell monolayers. In addition, TAX suppressed the phosphorylation of nuclear factor kappa-B (NF-κB), inhibitor protein of NF-κBα (IκBα), and myosin light chain (MLC), and downregulated the expression of myosin light chain kinase (MLCK) in LPS-treated Caco-2 cells. In summary, TAX can maintain TJ proteins by inhibiting the NF-κB/MLCK pathway and pro-inflammatory factor secretion to ameliorate LPS-induced intestinal epithelial barrier dysfunction. Thus, TAX is a promising candidate agent for use in functional food to ameliorate intestinal barrier dysfunction.
肠上皮屏障功能障碍可引发多种肠道疾病。黄酮类化合物已被证明对肠上皮屏障功能有益。然而，二氢槲皮素（TAX）作为一种天然存在的黄酮类化合物，对肠上皮屏障功能的影响尚不清楚。因此，本研究旨在探讨 TAX 对脂多糖（LPS）诱导的 Caco-2 细胞单层模型中肠上皮屏障功能障碍的保护作用及其潜在机制。我们的结果表明，TAX 增加了跨上皮电阻（TEER）并降低了受损肠上皮屏障中荧光素异硫氰酸酯（FITC）-葡聚糖（4 kDa）的通量。同时，TAX 抑制 LPS 诱导的紧密连接（TJ）蛋白（Claudin-1、ZO-1 和 Occludin）mRNA 和蛋白表达降低，并改善 TJ 连续分布模式的破坏。这些结果表明 TAX 改善了肠上皮屏障功能障碍。关于潜在机制，TAX 减少了 LPS 诱导的 Caco-2 细胞单层中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β 和 IL-6 的分泌。此外，TAX 抑制 LPS 处理的 Caco-2 细胞中核因子 kappa-B（NF-κB）、NF-κBα 抑制剂蛋白（IκBα）和肌球蛋白轻链（MLC）的磷酸化，并下调肌球蛋白轻链激酶（MLCK）的表达。总之，TAX 通过抑制 NF-κB/MLCK 通路和促炎因子的分泌来维持 TJ 蛋白，从而改善 LPS 诱导的肠上皮屏障功能障碍。因此，TAX 是一种有前途的候选药物，可用于功能性食品以改善肠道屏障功能障碍。
