Enhancement of epithelial cell autophagy induced by sinensetin alleviates epithelial barrier dysfunction in colitis

• Published in: Pharmacological research 2019-10, Vol.148, p.104461-104461, Article 104461
• Main Authors: Xiong, Yong-jian, Deng, Zhao-bin, Liu, Jia-ni, Qiu, Juan-juan, Guo, Li, Feng, Pan-pan, Sui, Jing-ru, Chen, Da-peng, Guo, Hui-shu
• Format: Article
• Language: English
• Subjects: Colitis; Epithelial autophagy; Epithelial barrier loss; Sinensetin
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2019.104461

[Display omitted] Intestinal epithelial barrier dysfunction is a key pathology of colitis. Autophagy of epithelial cells maintains homeostasis of the intestinal barrier by inhibiting apoptosis and stimulating degradation of the tight junction protein claudin-2. This study investigated the effects and mechanism of activity of sinensetin, a polymethylated flavonoid isolated from tangerine peel and citrus, on intestinal barrier dysfunction in colitis. Animal model of colitis were established by intracolonic administration of 2, 4, 6-trinitrobenzene sulfonic acid and oral treatment with dextran sulfate sodium. Epithelial barrier function was evaluated by measuring the serum recovery of fluorescein isothiocyanate-4 kD dextran in vivo and transepithelial electrical resistance in Caco-2 cells, respectively. Epithelial cell autophagy assayed by autophagosome formation and expression of autophagy-related protein. Sinensetin reversed colitis-associated increase in intestinal permeability, significantly promoted epithelial cell autophagy, and further decreased epithelial cell apoptosis, and reduced mucosal claudin-2. Sinenstetin alleviated colitis symptoms rats and mice with colitis. Knockdown of 5′ adenosine monophosphate-activated protein kinase (AMPK) reversed the promotion of epithelial autophagy by sinensetin. In conclusion, sinensetin significantly alleviated intestinal barrier dysfunction in colitis by promoting epithelial cell autophagy, and further inhibiting apoptosis and promoting claudin-2 degradation. The results highlighted novel potential benefits of sinensetin in colitis.