Wei Chang An pill alleviates 2,4,6-trinitro-benzenesulfonic acid-induced ulcerative colitis by inhibiting epithelial-mesenchymal transition process

Abstract

Objective: To investigate the inhibitory effect and mechanism of Wei Chang An pill (WCA) on ulcerative colitis (UC). Methods: A 2,4,6-trinitro-benzenesulfonic acid (TNBS)-induced UC model was established, and WCA was administered orally for 1 week. Body weight, colon length, disease activity index (DAI) score, and colon mucosa damage index (CMDI) score were recorded. Cytokine expression in lipopolysaccharide (LPS)-stimulated THP-1 cells was evaluated to determine the anti-inflammatory effects of WCA and its active ingredients. Immunohistochemistry and immunofluorescence were performed to detect the expression of epithelial-mesenchymal transition (EMT) markers E-cadherin and vimentin in rat UC and WCA groups, and in Caco-2 cells stimulated with conditioned medium (CM) from THP-1 cells, with or without LPS or WCA. Results: WCA significantly inhibited body weight loss, decreased DAI and CMDI scores, blocked colon length shortening, and improved histological damage in UC rats. Furthermore, both myeloperoxidase (MPO) activities and cytokine expression in UC tissues were significantly suppressed by WCA as well. In THP-1 cells, the mRNA expression of interferon-inducible protein (IP)-10, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and NF-κB inhibitor α (IκBα) was significantly suppressed by WCA and its active ingredients. E-cadherin expression in UC rats and CM-stimulated Caco-2 cells was downregulated and vimentin expression was upregulated, whereas both were blocked when administered with WCA. Conclusions: Our data showed that WCA alleviated UC progression by inhibiting inflammation-induced EMT progression. Graphical abstract: http://links.lww.com/AHM/A56