3,4-Methylenedioxy-beta-Nitrostyrene Alleviates Dextran Sulfate Sodium-Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome

Inflammatory bowel disease (IBD) has been reported to be associated with NLRP3 inflammasome activation. Therefore inhibiting inflammasome activation could be a new approach to treat IBD. Inflammasome inhibitors NLRP3-IN-2, JC124, and 3,4-methylenedioxy-beta-nitrostyrene (MNS) were previously reported to exert anti-inflammatory effects in various disease models but not in the dextran sulfate sodium (DSS)-induced colitis model. Here, we showed that MNS was more efficient in inhibiting the secretion of interleukin-1 beta (IL-1 beta) by blocking oligomerization of apoptosis-associated speck-like protein (ASC) than NLRP3-IN-2 and JC124. To investigate the protective effects of MNS on enteritis, we administered intragastric MNS to DSS-induced colitis mice. The results demonstrated that MNS attenuated DSS-induced body weight loss, colon length shortening, and pathological damage. In addition, MNS inhibited the infiltration of macrophages and inflammatory cells and reduced IL-1 beta and IL-12p40 pro-inflammatory cytokines but had no significant effect on tumor necrosis factor alpha (TNF-alpha) and IL-6. Furthermore, we also found that the differentiation of IL-17A(+)interferon-gamma (IFN-gamma)(+)CD4(+) T cell was decreased in the colon after MNS treatment, which might be mediated by IL-1 beta, etc. cytokine release. Taken together, MNS alleviated DSS-induced intestinal inflammation by inhibiting NLRP3 inflammasome activation, which may function as an effective therapeutic for IBD.