Oxymatrine Attenuates Ulcerative Colitis through Inhibiting Pyroptosis Mediated by the NLRP3 Inflammasome

• DOI: 10.3390/molecules29122897
• Publication Date: 2024-06-19T08:21:28Z
• Authors: Jing Sun; Shuai Wang; Zhengtian Zhao; Jiaqi Lu; Yiming Zhang; Wen An; Wei Li; Li Yang; Xiaowei Tong
• Keywords: Pyroptosis; Pyrin domain; Proinflammatory cytokine

Ulcerative colitis (UC) is difficult to cure and easy relapse, leading poor quality of life for patients. Oxymatrine (OMT) one the main alkaloids Sophora flavescens Aiton, which has many effects, such as anti-inflammation, anti-oxidative stress, immunosuppression. This study aimed investigate whether OMT could attenuate ulcerative by inhibiting NOD-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis. In this study, UC rat models were established 2,4,6-Trinitrobenzenesulfonic acid (TNBS) in vivo, while RAW264.7 cells peritoneal macrophages stimulated with Lipopolysaccharides/Adenosine Triphosphate (LPS/ATP) vitro simulate pyroptosis models, Western blotting (WB) other detection techniques applied analyze proteins involved NLRP3 inflammasome pathway. Our results showed that alleviated ulcers pathological damage TNBS-induced rats exhibited an inhibitory effect on at early stage UC. model group, reached peak 24 h after modeling contents active-cysteine-aspartic proteases-1 (caspase-1), Gasdermin D (GSDMD)-N, cleaved-interleukin-1 beta (IL-1β) highest expression level. Meanwhile, we found (80 mg kg−1) remarkably decreased levels NLRP3, active-caspase-1, cleaved-IL-1β lesion tissue from rats. Further experiments demonstrated concentrations 100 250 μM significantly inhibited cell death caused activation (p < 0.05), downregulated caspase-1, GSDMD, GSDMD-N, RAW326.7 cells, macrophages. summary, these indicated through mediated inflammasome. The inhibition may be a potential strategy