Hwang Hye-Jeong, Lee So Rok, Yoon Ju-Gyeong, Moon Hye-Ri, Zhang Jingnan, Park Eunmi, Yoon Su-In, Cho Jin Ah
Department of Agrofood Resources, National Institute of Agricultural Sciences, Rural Development Administration, Wanju 55365, Korea.
Department of Food and Nutrition, Chungnam National University, 99, Daehak-ro, Yuseong-gu, Daejeon 34134, Korea.
Antioxidants (Basel). 2022 Jul 26;11(8):1448. doi: 10.3390/antiox11081448.
The intestinal epithelial barrier is the primary and most significant defense barrier against ingested toxins and pathogenic bacteria. When the intestinal epithelium barrier is breached, inflammatory response is triggered. GWAS data showed that endoplasmic reticulum (ER) stress markers are elevated in Inflammatory Bowel Disease (IBD) patients, which suggests ER stress regulation might alleviate IBD symptoms. Ferulic acid (FA) is a polyphenol that is abundant in plants and has antioxidant and anti-inflammatory properties, although it is unclear whether FA has these effects on the intestine. Therefore, we investigated the effect of FA in vitro and in vivo. It was found that FA suppressed ER stress, nitric oxide (NO) generation, and inflammation in polarized Caco-2 and T84 cells, indicating that the ER stress pathway was implicated in its anti-inflammatory activities. The permeability of polarized Caco-2 cells in the presence and absence of proinflammatory cytokines were decreased by FA, and MUC2 mRNA was overexpressed in the intestines of mice fed a high-fat diet (HFD) supplemented with FA. These results suggest that FA has a protective effect on intestinal tight junctions. In addition, mouse intestine organoids proliferated significantly more in the presence of FA. Our findings shed light on the molecular mechanism responsible for the antioxidant effects of FA and its protective benefits on the health of the digestive system.
肠道上皮屏障是抵御摄入毒素和病原菌的主要且最重要的防御屏障。当肠道上皮屏障被破坏时，就会引发炎症反应。全基因组关联研究（GWAS）数据显示，内质网（ER）应激标志物在炎症性肠病（IBD）患者中升高，这表明内质网应激调节可能会减轻IBD症状。阿魏酸（FA）是一种在植物中含量丰富的多酚，具有抗氧化和抗炎特性，不过FA对肠道是否有这些作用尚不清楚。因此，我们在体外和体内研究了FA的作用。结果发现，FA抑制了极化的Caco-2和T84细胞中的内质网应激、一氧化氮（NO）生成及炎症，这表明内质网应激途径与其抗炎活性有关。在存在和不存在促炎细胞因子的情况下，FA均降低了极化的Caco-2细胞的通透性，并且在补充了FA的高脂饮食（HFD）喂养的小鼠肠道中，MUC2 mRNA表达上调。这些结果表明，FA对肠道紧密连接具有保护作用。此外，在有FA存在的情况下，小鼠肠道类器官的增殖明显更多。我们的研究结果揭示了FA抗氧化作用及其对消化系统健康保护益处的分子机制。
