Kuijie decoction ameliorates ulcerative colitis by affecting intestinal barrier functions, gut microbiota, metabolic pathways and Treg/Th17 balance in mice

• Published in: Journal of ethnopharmacology 2024-01, Vol.319 (Pt 3), p.117316-117316, Article 117316
• Main Authors: Peng, Kaixin, Xia, Suhong, Xiao, Siqi, Zhang, Mingyu, Liao, Jiazhi, Yu, Qin
• Format: Article
• Language: English
• Subjects: Animals; Body Weight; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Gastrointestinal Microbiome; Gut microbiota; Kuijie decoction; Medicine, Chinese Traditional; Metabolic Networks and Pathways; Mice; Microbial metabolites; RNA, Ribosomal, 16S; T-Lymphocytes, Regulatory; Th17 Cells; Th17/Treg balance; Ulcerative colitis
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2023.117316

Currently, the clinical treatment is limited and difficult to achieve satisfactory results for ulcerative colitis (UC). The role of traditional Chinese medicine (TCM) in the treatment of UC is very complex. Kuijie decoction (KJD) as a classic TCM, is widely used in the clinical treatment of UC, but the mechanism of its action is still unclear. This study is to investigate the protective effects of KJD on UC and the underlying mechanisms. The experimental model of UC was induced by DSS, and KJD was introduced into the model at the same time. Clinical symptoms, including the body weight, colon length and colon histopathological, were used to measure the severity of colitis. The expression of inflammatory cytokines and tight junction proteins was quantified. The effect of KJD on intestinal flora and intestinal metabolism was determined by 16S rRNA and untargeted metabolomics analysis, respectively. The proportion of Th17 cells and Tregs in the spleen was examined by flow cytometry. Mice treated with KJD showed significantly alleviated clinical symptoms and histological damage, such as more body weight gain, lower disease activity index (DAI) score, and longer colon length. The administration of KJD also led to the down-regulation of inflammatory mediators, upregulation of the expression of ZO-1, occludin and decreased claudin-2, as well as altered microbiota composition against DSS challenges (especially an increase of Lachnospiraceae). KJD enhanced the percentage of Treg cells but decreased the proportion of Th17 cells to maintain intestinal homeostasis by improving gut microbiota metabolism. In summary, KJD maintained intestinal epithelial homeostasis by regulating epithelial barrier function, intestinal flora, and restoring Th17/Treg balance. KJD has the potential to be a Chinese medicine treatment for UC. KJD dramatically relieved DSS-induced UC by maintaining intestinal homeostasis, such as restoring epithelial barrier function and reducing inflammation infiltration. The maintenance of homeostasis devoted to altering the diversity and richness of intestinal flora especially the increase of Lachnospiraceae, as well as promoting Th17 Tregs balance by the amino acid metabolites of intestinal flora. [Display omitted] •KJD ameliorates DSS-induced ulcerative colitis.•KJD dramatically restores epithelial barrier function and reduces inflammation infiltration.•KJD regulates the intestinal flora especially the increase of Lachnospiraceae and Th17/Tregs balance.