Yuan Jinwen, Che Siyan, Zhang Li, Ruan Zheng
State Key Laboratory of Food Science and Technology, Nanchang Key Laboratory of Fruits and Vegetables Nutrition and Processing, Institute of Nutrition and School of Food Science, Nanchang University, Nanchang 330047, China.
J Agric Food Chem. 2021 Apr 14;69(14):4101-4110. doi: 10.1021/acs.jafc.1c00199. Epub 2021 Mar 22.
Luteolin, a dietary flavonoid, has gained increasing interest as an intestinal protectant. This study aimed to evaluate the reparative effect of luteolin against ethanol-induced intestinal barrier damage in a Caco-2 cell monolayer model and the potential mechanisms. Luteolin attenuated ethanol-induced intestinal barrier injury, by increasing transepithelial monolayer resistance (TEER, 27.75 ± 14.75% of the ethanol group, < 0.01), reducing Lucifer yellow flux (13.21 ± 1.23% of ethanol group, < 0.01), and upregulating the expression of tight junction (TJ) proteins zonulin occludin-1 (ZO-1), occludin, and claudin-1 (37.963 ± 8.62%, 17.69 ± 7.35%, and 29.40 ± 8.08% of the ethanol group, respectively, < 0.01). Further mechanistic studies showed that luteolin suppressed myosin light chain 2 (MLC) phosphorylation, myosin light chain kinase (MLCK) activation, nuclear factor kappa-B (NF-κB) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Moreover, luteolin also acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation to relieve ethanol-induced oxidative damage and TJ dysfunction. The results of the study indicate that luteolin may play an effective role in relieving intestinal barrier damage, and this effect is at least partially due to its indirect antioxidant capacity.
木犀草素是一种膳食类黄酮，作为一种肠道保护剂越来越受到关注。本研究旨在评估木犀草素对乙醇诱导的Caco-2细胞单层模型肠道屏障损伤的修复作用及其潜在机制。木犀草素通过增加跨上皮单层电阻（TEER，为乙醇组的27.75±14.75%，P<0.01）、降低荧光素黄通量（为乙醇组的13.21±1.23%，P<0.01）以及上调紧密连接（TJ）蛋白zonulin、闭合蛋白-1（ZO-1）、闭合蛋白和Claudin-1的表达（分别为乙醇组的37.963±8.62%、17.69±7.35%和29.40±8.08%，P<0.01）来减轻乙醇诱导的肠道屏障损伤。进一步的机制研究表明，木犀草素可抑制肌球蛋白轻链2（MLC）磷酸化、肌球蛋白轻链激酶（MLCK）激活、核因子κB（NF-κB）核转位以及丝裂原活化蛋白激酶（MAPK）磷酸化。此外，木犀草素还通过上调抗氧化反应元件（ARE）和核因子（红系衍生2）样2（Nrf2）核转位间接发挥抗氧化剂的作用，以减轻乙醇诱导的氧化损伤和TJ功能障碍。研究结果表明，木犀草素可能在减轻肠道屏障损伤方面发挥有效作用，且这种作用至少部分归因于其间接抗氧化能力。
