Kurarinone and Nor-kurarinone inhibit NLRP3 inflammasome activation and regulate macrophage polarization against ulcerative colitis.

Activation of NOD-like receptor protein 3 (NLRP3) can lead to the production of inflammatory factors and perturbation of macrophage polarization, leading to an intestinal immune imbalance that promotes the progression of ulcerative colitis (UC). In this study, we investigated the therapeutic effect of Kurarinone and Nor-kurarinone on UC and their regulatory mechanisms relating to NLRP3 inflammasome activation and macrophage polarization. UC mice were induced using dextran sulfate sodium (DSS) and treated with Kurarinone and Nor-kurarinone. Results showed that Kurarinone and Nor-kurarinone could alleviate weight loss, decrease the disease activity index (DAI) score, shorten colon length, inhibit formation of the NLRP3 inflammasome in the colon and regulate macrophage polarization in UC mice. The THP-1 cells were used as an in vitro model of the NLRP3 inflammasome, conducted by treatment with lipopolysaccharide (LPS) and ATP/Nigericin. Kurarinone and Nor-kurarinone can inhibit the NLRP3 inflammasome formation response by disrupting the NLRP3/ASC interaction to inhibit NLRP3 assembly and then regulating the polarization of macrophages. In conclusion, Kurarinone and Nor-kurarinone inhibited NLRP3 inflammasome assembly to counteract activation of the NLRP3 inflammasome. This inhibition led to a reduction in M1 polarization of intestinal macrophages in UC mice to keep the balance of M1/ M2 macrophages. Our study suggests that Kurarinone and Nor-kurarinone may be novel therapeutic modalities for UC.