Munronoid I Ameliorates DSS-Induced Mouse Colitis by Inhibiting NLRP3 Inflammasome Activation and Pyroptosis Via Modulation of NLRP3.

Abstract

Inflammatory bowel diseases (IBDs) are increasingly common diseases characterized by chronic and relapsing inflammation of the gastrointestinal tract. NLRP3 might be a crucial regulator of the homeostatic balance of the intestine, but its upregulation leads to pyroptosis. Munronoid I is extracted and purified from Munronia sinica, which has shown an anti-inflammatory effect, but the efficacy of Munronoid I in IBD remains unproven. In this study, we attempted to determine the effect of Munronoid I on NLRP3 to regulate the inflammasome activation and pyroptosis in IBD. Our data demonstrated that Munronoid I treatment attenuated DSS-induced body weight loss, pathological injury of the colon, the production of IL-1β and IL-18, and the expression of pyroptosis-associated proteins in colon tissue in mice. Moreover, Munronoid I inhibited LPS/ATP-induced pyroptosis in mouse peritoneal macrophages, MODE-K cells, and DSS-induced pyroptosis in mouse colonic epithelial cells, and decreased the release of inflammatory cytokines IL-1β and IL-18 in mouse peritoneal macrophages. Mechanically, Munronoid I could suppress the NLRP3 inflammasome activation and pyroptosis by promoting the K48-linked ubiquitination and NLRP3 degradation. It is suggested that Munronoid I might be a potential therapeutic candidate for IBD.

• Authors: Xingyu Ma, Qianqian Di, Xiaoli Li, Xibao Zhao, Ruihan Zhang, Yue Xiao, Xunwei Li, Han Wu, Haimei Tang, Jiazheng Quan, Zherui Wu, Weilie Xiao, Weilin Chen
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 853194 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35865528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Ma, Di, Li, Zhao, Zhang, Xiao, Li, Wu, Tang, Quan, Wu, Xiao and Chen.

Chemical References

• Inflammasomes
• Interleukin-18
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Dextran Sulfate

Topics

• Animals
• Colitis (pathology)
• Dextran Sulfate (adverse effects)
• Inflammasomes (metabolism)
• Inflammatory Bowel Diseases (metabolism)
• Interleukin-18 (pharmacology)
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Pyroptosis