引言：尽管芥酸存在于多种可食用植物中，并且已经证实其具有抗炎特性，包括治疗结肠炎，但其作用机制和对肠道微生物组成的影响尚不清楚。本研究旨在找到一个早期应答激酶，该激酶调节紧密连接蛋白的定位，作用于炎症反应的开始，并受芥酸调控。此外，我们还分析了芥酸对肠道微生物组稳态的影响。方法：我们在完全分化的Caco-2细胞中进行了芥酸处理2小时后的早期应答基因的异常改变研究，这些基因包括核因子κB（NF-κB）和激活转录因子（ATF）-2，在有或没有脂多糖和肿瘤坏死因子（TNF）-α刺激的情况下。为了确认芥酸对刺激诱导紧密连接蛋白，包括ZO-1、occludin和claudin-2的定位异常的影响，我们分析了从Caco-2细胞和小鼠肠道中提取的膜蛋白和细胞质蛋白的部分。使用2％的硫酸葡聚糖诱导C57BL/6小鼠发生结肠炎，并且给予芥酸（2或10mg/kg/天）治疗15天。此外，对芥酸在治疗炎症性肠病（IBD）中的营养药物和药理活性进行了评估。结果：我们确认了芥酸在体外和体内显著抑制刺激诱导的紧密连接蛋白从肠道细胞膜上的定位异常和肠道通透性，以及白细胞介素（IL）-1β和TNF-α等炎症因子的表达。我们发现芥酸直接与转化生长因子β激活激酶1（TAK1）结合，并抑制刺激诱导的NF-κB和MAPK/ATF-2通路的活化，从而调节丝裂原活化蛋白激酶（MLCK）的表达。膳食芥酸还改善了肠道微生物组的不平衡和炎症性肠病症状，在结肠炎小鼠中表现为肠道长度和形态的改善。讨论：这些发现表明，芥酸可能是一种针对TAK1并抑制NF-κB和ATF-2信号的有效营养药物和药理治疗剂，用于治疗炎症性肠病。版权所有 © 2023 Jang、Kim、So、Kim、Kim、Lee和Jung。

Introduction: Although sinapic acid is found in various edible plants and has been shown to have anti-inflammatory properties including colitis, its underlying mechanism and effects on the composition of the gut microbiota are largely unknown. We aimed to identify an early response kinase that regulates the localization of tight junction proteins, act at the onset of the inflammatory response, and is regulated by sinapic acid. Additionally, we analyzed the effects of sinapic acid on the homeostasis of the intestinal microbiome. Methods: We examined the aberrant alterations of early response genes such as nuclear factor-kappa B (NF-κB) and activating transcription factor (ATF)-2 within 2 h of sinapic acid treatment in fully differentiated Caco-2 cells with or without lipopolysaccharide and tumor necrosis factor (TNF)-α stimulation. To confirm the effect of sinapic acid on stimulus-induced delocalization of tight junction proteins, including zonula occludens (ZO)-1, occludin, and claudin-2, all tight junction proteins were investigated by analyzing a fraction of membrane and cytosol proteins extracted from Caco-2 cells and mice intestines. Colitis was induced in C57BL/6 mice using 2% dextran sulfate sodium and sinapic acid (2 or 10 mg/kg/day) was administrated for 15 days. Furthermore, the nutraceutical and pharmaceutical activities of sinapic acid for treating inflammatory bowel disease (IBD) evaluated. Results: We confirmed that sinapic acid significantly suppressed the stimulus-induced delocalization of tight junction proteins from the intestinal cell membrane and abnormal intestinal permeability as well as the expression of inflammatory cytokines such as interleukin (IL)-1β and TNF-α in vitro and in vivo. Sinapic acid was found to bind directly to transforming growth factor beta-activated kinase 1 (TAK1) and inhibit the stimulus-induced activation of NF-κB as well as MAPK/ATF-2 pathways, which in turn regulated the expression of mitogen-activated protein kinase (MLCK). Dietary sinapic acid also alleviated the imbalanced of gut microbiota and symptoms of IBD, evidenced by improvements in the length and morphology of the intestine in mice with colitis. Discussion: These findings indicate that sinapic acid may be an effective nutraceutical and pharmaceutical agent for IBD treatment as it targets TAK1 and inhibits subsequent NF-κB and ATF-2 signaling.Copyright © 2023 Jang, Kim, So, Kim, Kim, Lee and Jung.