TXM-CB13 Improves the Intestinal Mucosal Barrier and Alleviates Colitis by Inhibiting the ROS/TXNIP/TRX/NLRP3 and TLR4/MyD88/NF-κB/NLRP3 Pathways

• DOI: 10.1007/s10753-025-02282-9
• Publication Date: 2025-03-14T07:25:50Z
• Authors: Ruijie Cao; Jinhui Zhou; Jiale Liu; Yaxuan Wang; Yandong Dai; Yun Jiang; Akira Yamauchi; Daphne Atlas; Tiancheng Jin; Jiedong Zhou; Cuixue Wang; Qihuan Tan; Yifei Chen; Junji Yodoi; Hai Tian
• Keywords: Occludin

The activation of inflammasomes (NLRP3 and NLRP1) is central to the pathogenesis inflammatory bowel disease (IBD). Here we examined protective effects a thioredoxin-mimetic peptide CB13 (TXM-CB13), known for its antioxidative stress anti-inflammatory properties. We TXM-CB13 on dextran sulfate sodium (DSS)-induced colitis lipopolysaccharide (LPS)-induced NLRP3 inflammasome in RAW264.7 macrophages. appeared alleviate symptoms DSS-induced significantly suppress protein mRNA levels NLRP3, Mlck, IL-1β colonic tissues. Additionally, treatment increased intestinal barrier proteins Occludin, ZO-1, NLRP1, as shown through immunohistochemistry Western blot analysis. In vitro, inhibited LPS-induced TLR4 signaling, reducing MyD88 consequently attenuating NF-κB pathways, including p-IκB-α/IκB-α p-NF-κB-p65/NF-κB-p65. This inhibition further reduced components, ASC, Caspase-1, GSDMD, IL-1β. addition, prevented ROS-mediated dissociation TXNIP from TRX, inhibiting activation. These findings suggest that potential therapeutic candidate IBD modulation TLR4/MyD88/NF-κB/NLRP3 ROS/TXNIP/TRX/NLRP3 pathways.