Beneficial Effects of Celastrol on Immune Balance by Modulating Gut Microbiota in Experimental Ulcerative Colitis Mice

Mingyue Li, Weina Guo, Yalan Dong, Wenzhu Wang, Chunxia Tian, Zili Zhang, Ting Yu, Haifeng Zhou, Yang Gui, Kaming Xue, Junyi Li, Feng Jiang, Alexey Sarapultsev, Huafang Wang, Ge Zhang, Shanshan Luo, Heng Fan, Desheng Hu*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

8 Citations (Scopus)

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis. Previous studies have indicated that celastrol (CSR) has strong anti-inflammatory and immune-inhibitory effects. Here, we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model, and addressed the mechanism by which CSR exerts the protective effects. We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining, intestinal permeability assay, cytokine assay, flow cytometry, fecal microbiota transplantation (FMT), 16S rRNA sequencing, untargeted metabolomics, and cell differentiation. CSR administration significantly ameliorated the dextran sodium sulfate (DSS)-induced colitis in mice, which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index (DAI) score and intestinal permeability. Meanwhile, CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels, and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis. Notably, all the therapeutic effects were exerted in a gut microbiota-dependent manner. Furthermore, CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites, which is probably associated with the gut microbiota-mediated protective effects. In conclusion, this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.

Original languageEnglish
Pages (from-to)288-303
Number of pages16
JournalGenomics, Proteomics and Bioinformatics
Volume20
Issue number2
DOIs
Publication statusPublished - Apr 2022

Scopus Subject Areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Computational Mathematics

User-Defined Keywords

  • Ulcerative colitis
  • Celastrol
  • Gut microbiota
  • Treg/Th balance
  • Metabolomics

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