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

Area of Science:

• Immunology
• Gastroenterology
• Pharmacology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory disease with a high risk of colon cancer and disability.
• Current immunoregulatory therapies for UC have unsatisfactory remission rates.
• Si-Ni-San (SNS), a traditional remedy, shows clinical efficacy in UC, but its mechanisms are unclear.

Purpose of the Study:

• To investigate the therapeutic effects of SNS on chronic colitis development.
• To elucidate the underlying molecular mechanisms of SNS in colitis.

Main Methods:

• A dextran sulfate sodium (DSS)-induced chronic experimental colitis mouse model was utilized.
• RNA sequencing and bioinformatic analysis were performed to identify molecular targets.
• In vitro studies were conducted to validate signaling pathway modulation.

Main Results:

• SNS significantly ameliorated experimental colitis by inhibiting inflammatory gene expression.
• SNS suppressed type I interferon (IFN) responses, rather than directly reducing pro-inflammatory cytokines like IL-6.
• SNS selectively inhibited STING and RIG-I pathway-induced type I IFN responses via TBK1/IRF3 signaling and STAT1/STAT2 activation.

Conclusions:

• Type I IFN responses play a significant pathogenic role in colitis.
• SNS or its derived compounds may offer novel therapeutic strategies for UC.
• Interfering with type I IFN-mediated inflammation is a promising approach for UC treatment.