P20 The novel compound HLY effectively relieves ulcerative colitis by xbp1-myh9 pathway

Abstract

Ulcerative colitis (UC) is a recurrent and chronic intestinal disease. Available drugs for UC are accompanied by poor effectiveness or severe adverse events and thus there is an urgent need to develop specific and effective drugs for UC treatment. HLY is a new compound synthesised from coptisine by our institute. HLY activates the transcriptional activity of X-box binding protein 1 (xbp1) and inhibits the expression of non-muscle myosin heavy chain 9 (myh9) in intestinal epithelial cells (IEC6). When the xbp1 gene was silenced by siRNA, HLY had no effect on myh9. HLY effectively reduced body weight loss and the percentage of colon contracture in vivo , decreased disease activity index (DAI) score, colon mucosal damage index (CMDI) and tissue histopathological index (THI) in dextran sulfate sodium (DSS)-induced UC mice. Furthermore, oral HLY effectively increased the expression of xbp1 and inhibited the expression of myh9 in vivo as demonstrated by western-blot and immunohistochemical assays. Taken together, HLY could alter ulcerative colitis via the xbp1-myh9 pathway. To our knowledge, this is the first report demonstrating that the monomer compound targets the xbp1-myh9 pathway in the treatment of UC. HLY may be developed as a possible therapeutic candidate for UC.