Polyphenol Rich Extract Alleviates DSS-Induced Ulcerative Colitis in Mice through the Nrf2-NLRP3 Pathway.

This study systematically evaluated the effect of extract on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) and determined its mechanism of action. The results showed that extract significantly inhibited DSS-induced UC in mice. In vivo mechanistic studies revealed that extract relieved the symptoms of colitis by enhancing antioxidant activity and inhibiting pyroptosis. Further in vitro experiments on the mechanism of showed that it reduced the level of reactive oxygen species (ROS) in J774A.1 cells. We found that extract enhanced cellular antioxidation activity and inhibited pyroptosis. After silencing NLRP3, it was found to play an important role in pyroptosis. In addition, after Nrf2 was silenced, the inhibitory effect of extract on cell pyroptosis was eliminated, indicating an interaction between Nrf2 and NLRP3. Metabonomics revealed that extract significantly improved metabolic function in colitis mice by reversing the abnormal changes in the levels of 9 metabolites. The main metabolic pathways involved were glutathione metabolism, aminoacyl-tRNA biosynthesis and linoleic acid metabolism. In conclusion, we found that extract significantly alleviated DSS-induced UC injury through the Nrf2-NLRP3 pathway and relieved metabolic dysfunction.