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

Abstract

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-β-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-1β (IL-1β) 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-1β and IL-12p40 pro-inflammatory cytokines but had no significant effect on tumor necrosis factor α (TNF-α) and IL-6. Furthermore, we also found that the differentiation of IL-17A+interferon-γ (IFN-γ)+CD4+ T cell was decreased in the colon after MNS treatment, which might be mediated by IL-1β, 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.

• Authors: Juanjuan Zheng, Zhongxin Jiang, Yue Song, Shu Huang, Yuzhang Du, Xiaobao Yang, Yan Xiao, Zhihui Ma, Dakang Xu, Jing Li
• Journal: Frontiers in pharmacology (Front Pharmacol) Vol. 13 Pg. 866228 ( 2022) ISSN: 1663-9812 [Print] Switzerland
• PMID: 35784693 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Zheng, Jiang, Song, Huang, Du, Yang, Xiao, Ma, Xu and Li.