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Enhancement of Epithelial Cell Autophagy Induced by Sinensetin Alleviates Epithelial Barrier Dysfunction in Colitis

Enhancement of Epithelial Cell Autophagy Induced by Sinensetin Alleviates Epithelial Barrier Dysfunction in Colitis

Yong-Jian Xiong, Zhao-Bin Deng, Jia-Ni Liu, Juan-Juan Qiu, Li Guo, Pan-Pan Feng, Jing-Ru Sui, Da-Peng Chen, Hui-Shu Guo

Pharmacol Res. 2019 Oct;148:104461.

PMID: 31542404

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2306276	Sinensetin		2306-27-6	Price

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