Development of an XBP1 agonist, HLJ2, as a potential therapeutic agent for ulcerative colitis
10.3867/j.issn.1000-3002.2017.10.041
- Author:
TANG XIAO-NAN
1
;
ZHANG HAI-JING
;
SONG GUANG-MING
;
SONG HUA-CHEN
;
WANG WEN-JIE
;
WU LIAN-QIU
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines
- Keywords:
ulcerative colitis;
XBP1;
intestinal flora;
intestinal mucosa;
cytokines
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(10):970-971
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis (UC), a recurrent and intractable inflammatory bowel disease. METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI). HLJ2 also decreased myelo?peroxidase(MPO) activity and reduced production of the inflammatory cytokines TNF- α, IL- 1β, andIL- 6. HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate (DSS) and increased the expression of ZO-1 and claudin-1. Fecal 16s rRNA high-throughput sequencing demon?strated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2, including increased abundance of probiotics such as Lachnospiraceae, Prevotellaceae, and Lactobacillaceae. At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microor?ganisms such as Bacteroidaceae, Porphyromonadaceae, Deferribacteraceae, and Pseudomonadaceae in HLJ2- treated mice compared with untreated mice. CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation, regulates the intestinal flora, and protects the intestinal mucosa. It is thus a potential therapeutic agent for ulcerative colitis.
