Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Phytother Res. 2022 Aug;36(8):3248-3264. doi: 10.1002/ptr.7495. Epub 2022 May 22.
Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway-mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor β (ERβ) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERβ knock down in the colons of mice with DSS-induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERβ/TRIM21/PHB1 pathway.
肠黏液屏障功能障碍与炎症性肠病 (IBD) 的发病机制密切相关。为了研究牛蒡子素（一种从牛蒡果实中分离出的植物雌激素）对结肠炎条件下肠黏液屏障的保护作用及其潜在机制。通过体外和体内实验研究了牛蒡子素对肠黏液屏障和杯状细胞凋亡的作用。牛蒡子素通过抑制凋亡增加杯状细胞数量来促进黏液分泌和维持黏液屏障的完整性。牛蒡子素选择性抑制线粒体途径介导的细胞凋亡。此外，牛蒡子素通过激活雌激素受体β（ERβ）阻断泛素化，从而提高 PHB1 蛋白水平，通过与 PHB1 竞争结合并破坏 TRIM21 与 PHB1 的结合，从而发挥作用。在 DSS 诱导的结肠炎小鼠的结肠中敲低 ERβ 会导致牛蒡子素和 DPN 对黏膜屏障的保护作用显著降低。牛蒡子素通过 ERβ/TRIM21/PHB1 通路抑制杯状细胞凋亡，维持黏液屏障的完整性。
