Si-Ni-San ameliorates chronic colitis by modulating type I interferons-mediated inflammation.

Yajie Cai, Bing Xu, Fei Zhou, Jianzhi Wu, Shuo Li, Qi Zheng, Yajing Li, Xiaojiaoyang Li, Feng Gao, Shifen Dong, Runping Liu

Phytomedicine : international journal of phytotherapy and phytopharmacology 2021 Apr

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Ulcerative colitis (UC) is a chronic relapsing inflammatory disease that markedly elevates the risk of colon cancers and results in disability. The disrupted immune homeostasis has been recognized as a predominant player in the pathogenesis of UC. However, the overall remission rate of current therapies based on immunoregulation is still unsatisfactory. Si-Ni-San (SNS) has been found effective in relieving UC through thousands of years of clinical practice, yet the specific mechanisms of the protective effect of SNS were not fully elucidated. We aim to investigate the therapeutic effects of SNS against the development of chronic colitis and the underlying mechanisms. We established a DSS-induced chronic experimental colitis mouse model to evaluate the effect of SNS. RNA-sequencing, bioinformatic analysis, and in vitro studies were performed to investigate the underlying mechanisms. Our data demonstrated that SNS significantly ameliorated chronic experimental colitis via inhibiting the expression of genes associated with inflammatory responses. Interestingly, SNS significantly suppressed DSS-induced type I interferon (IFN) responses instead of directly downregulating the production of pro-inflammatory cytokines, such as Il-6. In vitro study further found that SNS selectively inhibited STING and RIG-I pathway-induced type I IFN responses by modulating TBK1- and IRF3-dependent signaling transduction. SNS also suppressed the expression of IFN-stimulated genes by directly inhibiting STAT1 and STAT2 activation. Our study not only provides novel insights into the pathogenic role of type I IFN responses in colitis but also suggested that SNS or bioactive compounds derived from SNS may serve as novel therapeutic strategies for the treatment of UC via interfering type I IFN-mediated inflammation. Copyright © 2021. Published by Elsevier GmbH.

Citation

Yajie Cai, Bing Xu, Fei Zhou, Jianzhi Wu, Shuo Li, Qi Zheng, Yajing Li, Xiaojiaoyang Li, Feng Gao, Shifen Dong, Runping Liu. Si-Ni-San ameliorates chronic colitis by modulating type I interferons-mediated inflammation. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021 Apr;84:153495