2',4'-dihydroxychalcone alleviates inflammatory bowel disease by inhibiting NLRP3 inflammasome and modulating gut microbiota.

2',4'-DHC exhibited the most remarkable inhibitory effect on NLRP3 inflammasome activation among 25 main ingredients of Abrus cantoniensis Hance.

• Screening was performed across 25 main ingredients from Abrus cantoniensis Hance (ACH).
• THP-1 and J774A.1 macrophage models were used to assess NLRP3 inflammasome inhibitory activity.
• 2',4'-DHC was identified as the lead compound with the most significant inhibitory activity.

2',4'-DHC selectively inhibited caspase-1 activation, Gasdermin D activation, and IL-1β release but not TNF-α in macrophages.

• ELISA and western blotting analyses were used to measure these inflammatory mediators.
• Caspase-1 and Gasdermin D activation were both effectively inhibited by 2',4'-DHC treatment.
• IL-1β release was significantly reduced, while TNF-α levels were not affected, indicating NLRP3-specific rather than general anti-inflammatory activity.
• Experiments were conducted in THP-1 and J774A.1 macrophage models.

2',4'-DHC significantly alleviated clinical symptoms in DSS-induced acute ulcerative colitis mice.

• A dextran sulfate sodium salt (DSS)-induced acute ulcerative colitis mouse model was used.
• 2',4'-DHC treatment mitigated body weight loss in colitis mice.
• The Disease Activity Index (DAI) score was reduced with 2',4'-DHC treatment.
• Colon length was preserved in 2',4'-DHC-treated colitis mice.

2',4'-DHC protected the gut barrier by enhancing expression of tight junction proteins occludin and ZO-1 in colitis mice.

• Expression levels of occludin and ZO-1 were assessed in the DSS-induced colitis mouse model.
• Both tight junction proteins showed enhanced expression following 2',4'-DHC treatment.
• Gut barrier protection was identified as a mechanism by which 2',4'-DHC alleviates IBD.

2',4'-DHC inhibited NLRP3 inflammasome activation in colitis mice in vivo.

• NLRP3 inflammasome inhibition was confirmed in the DSS-induced acute ulcerative colitis mouse model.
• This finding was consistent with in vitro results observed in macrophage models.
• NLRP3 inflammasome plays a crucial role in IBD pathogenesis according to the study background.

2',4'-DHC modulated gut microbiota composition in colitis mice by reducing Proteobacteria abundance and reshaping bacterial diversity.

• 16S rRNA analysis was performed for gut microbiota assessment.
• 2',4'-DHC treatment reduced the abundance of Proteobacteria in colitis mice.
• Bacterial diversity and composition were reshaped following 2',4'-DHC treatment.
• Gut microbiota modulation was identified as an additional mechanism contributing to the anti-inflammatory effects of 2',4'-DHC in IBD.