α-mangostin derivatives ameliorated mouse DSS-induced chronic colitis via regulating Th17/Treg balance

Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibitin...

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Published in:Molecular immunology 2024-02, Vol.166, p.110-118
Main Authors: Yang, Yuying, Deng, Yuqing, Zhang, Guoqiang, Xu, Xiaoting, Xiong, Xiaoxiao, Yu, Si, Peng, Fanrong, Tian, Xuyan, Ye, Weiying, Chen, Huanpeng, Yu, Bolan, Liu, Zhonghua, He, Xixin, Huang, Zhaofeng
Format: Article
Language:English
Subjects:
Animals
Colitis - chemically induced
Colitis - drug therapy
Colon
Dextran Sulfate - toxicity
Disease Models, Animal
IBD
Inflammation
Inflammatory Bowel Diseases
Mice
Mice, Inbred C57BL
T-Lymphocytes, Regulatory
Th17
Th17 Cells
Treg
Xanthones
α-mangostin
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Summary:Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibiting Th17 cell function. In our preliminary study, we obtained four derivatives by adding chemical modification of α-mangostin which could also inhibit Th17 cell differentiation in vitro. In this study, we constructed a chronic IBD mouse model and demonstrated the therapeutic effects of α-mangostin and its derivatives as therapeutic agents for IBD. In compounds treating groups, intestinal inflammation showed significant improvement in symptoms which included weight loss, high disease activity index, colon length shorten and the change of intestinal flora. We also found that compounds could effectively either suppress the number of Th17 cell or increase the number of Treg cell detected by flow cytometry, thus reducing the Th17/Treg ratio and suppressing the level of intestinal inflammation. Notably, IL17-F levels, rather than IL17-A, were reduced in the colon of mice of compounds treating groups. Thus, α-mangostin and its derivatives ameliorate DSS-induced chronic colitis in mice by regulating Th17/Treg balance to alleviate intestinal inflammation and can modulate the intestinal microbial community. These results suggest that α-mangostin and its derivatives may be the new therapeutic option for chronic colitis. •This study was explored the therapeutic effects of alpha-mangostin and its derivatives in IBD model.•α-mangostin and its derivatives regulate Th17/Treg balance and alleviate intestinal inflammation.•α-mangostin and its derivatives modulate the imbalance of intestinal microbial community.•This study provides a potential new drug for the treatment of IBD.
ISSN:0161-5890
1872-9142
DOI:10.1016/j.molimm.2023.11.013