Rosuvastatin and Engeletin Ameliorate Acetic Acid-Induced Ulcerative Colitis through Modulation of TXNIP/NLRP3-Related Inflammatory Signaling pathway

Mucosal inflammation is the defining feature of ulcerative colitis (UC), which is a chronic inflammatory bowel disease. The goal of this study was to determine the involvement of the TXNIP/NLRP3 inflammatory pathway in UC development and to assess the therapeutic potential of engeletin and rosuvastatin. Acetic acid (AA) was used to initiate UC. The animals were divided into seven groups: normal control, UC control, UC treated with mesalazine (100 mg/kg/day), UC treated with rosuvastatin (20 mg/kg/day), UC treated with engeletin (25 mg/kg/day), UC treated with engeletin (50 mg/kg/day), and UC treated with a combination of rosuvastatin and engeletin (20 mg and 25 mg/kg/day). All treatments lasted 21 days. Body weight, colon weight, colon length, and weight-to-length ratio were all assessed. ELISA was used to detect IL-1β, MPO, gasdermin-D, NF-κB p65, and TXNIP contents. TXNIP expression was quantified by quantitative real-time PCR, and colon samples were examined histopathologically and immunohistochemically. UC caused significant weight loss, increased colon weight, and a shift in the colon weight-to-length ratio. These changes were associated with elevated inflammatory markers and upregulation of the TXNIP/NLRP3 pathway markers. All measured parameters were significantly improved after treatment with engeletin, rosuvastatin, and their combination, with the combination having the most pronounced therapeutic benefits. In conclusion, this study demonstrated that AA-induced UC was associated with increased expression of TXNIP/NLRP3-related inflammatory markers, which may contribute to the disease pathophysiology. The combination of engeletin and rosuvastatin was associated with downregulation of TXNIP/NLRP3-related inflammatory signaling and amelioration of biochemical and histopathological changes associated with UC.