Cambogin suppresses dextran sulphate sodium‐induced colitis by enhancing Treg cell stability and function

• Published in: British journal of pharmacology Vol. 175; no. 7; pp. 1085 - 1099
• Main Authors: Lu, Yue, Kim, Na‐Mi, Jiang, Yi‐Wen, Zhang, Hong, Zheng, Dan, Zhu, Fu‐Xiang, Liang, Rui, Li, Bin, Xu, Hong‐Xi
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2018; John Wiley and Sons Inc
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Body weight; CD25 antigen; CD4 antigen; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - immunology; Colitis - pathology; Colon; Colon - drug effects; Colon - immunology; Colon - pathology; Cytokines - immunology; Dextran; Dextran Sulfate; Diarrhea; Enzyme-linked immunosorbent assay; Female; Forkhead Transcription Factors - immunology; Foxp3 protein; Gastrointestinal tract; HEK293 Cells; Histology; Humans; Immune response; Immunosuppressive agents; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory diseases; Interferon; Intestine; Leukocytes (mononuclear); Lipopolysaccharides; Lymph nodes; Lymphocytes T; Mice; Peripheral blood mononuclear cells; Research Paper; Research Papers; Rodents; Sodium; Spleen; Sulfates; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Terpenes - pharmacology; Terpenes - therapeutic use; Tumor necrosis factor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.14150

Background and Purpose Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, and an impaired immune response plays a critical role in IBD. The current drugs and therapies for IBD treatment are of limited use, therefore, there is a need to find novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)‐induced colitis and whether cambogin attenuates inflammation via a Treg‐cell‐mediated effect on the immune response. Experimental Approach Chronic colitis was established in mice using 2% DSS, and cambogin (10 mg·kg−1, p.o.) was administered for 10 days. Body weight, colon length and colon histology were assessed. Cytokine production was measured using elisa and quantitative real‐time PCR. To evaluate the mechanism of cambogin, human CD4+CD25hiCD127lo Treg cells were isolated from peripheral blood mononuclear cells. Major signalling profiles involved in Treg cell stability were measured. Key Results Cambogin attenuated diarrhoea, colon shortening and colon histological injury and IL‐6, IFN‐γ and TNF‐α production in DSS‐treated mice. Cambogin also up‐regulated Treg cell numbers in both the spleen and mesenteric lymph nodes. Furthermore, cambogin (10 μM) prevented Foxp3 loss in human primary Treg cells in vitro, and promoted USP7‐mediated Foxp3 deubiquitination and increased Foxp3 protein expression in LPS‐treated cells. Conclusions and Implications The effect of cambogin on DSS‐induced colitis is expedited by a Treg‐cell‐mediated modification of the immune response, suggesting that cambogin could be applied as a novel agent for treating colitis and other Treg cell‐related diseases.