Rosuvastatin and engeletin ameliorate acetic acid-induced ulcerative colitis through modulation of TXNIP/NLRP3-related inflammatory signaling pathway

Abstract

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.