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

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunopharmacology and Immunotoxicology Pub Date : 2026-09-02 DOI:10.1080/08923973.2026.2716666

Thanaa A El-Masry, Sally E Abu-Risha, Walaa A Negm, Eman Aly Kamal

{"title":"Rosuvastatin and engeletin ameliorate acetic acid-induced ulcerative colitis through modulation of TXNIP/NLRP3-related inflammatory signaling pathway.","authors":"Thanaa A El-Masry, Sally E Abu-Risha, Walaa A Negm, Eman Aly Kamal","doi":"10.1080/08923973.2026.2716666","DOIUrl":null,"url":null,"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.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"1-14"},"PeriodicalIF":3.1000,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunopharmacology and Immunotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08923973.2026.2716666","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

瑞舒伐他汀和恩来汀通过调节TXNIP/ nlrp53相关炎症信号通路改善醋酸诱导的溃疡性结肠炎。

溃疡性结肠炎（UC）是一种慢性炎症性肠病，粘膜炎症是溃疡性结肠炎（UC）的主要特征。本研究的目的是确定TXNIP/NLRP3炎症通路在UC发展中的作用，并评估恩格列素和瑞舒伐他汀的治疗潜力。醋酸（AA）引发UC。将动物分为7组：正常对照组、UC对照组、美萨拉嗪治疗UC （100 mg/kg/d）、瑞舒伐他汀治疗UC （20 mg/kg/d）、恩格列汀治疗UC （25 mg/kg/d）、恩格列汀治疗UC （50 mg/kg/d）、瑞舒伐他汀和恩格列汀联合治疗UC （20 mg和25 mg/kg/d）。所有治疗持续21 d。评估体重、结肠重量、结肠长度和体重与长度比。ELISA法检测小鼠IL-1β、MPO、gasdermin-D、NF-κB p65、TXNIP含量。采用实时荧光定量PCR检测TXNIP的表达，并对结肠标本进行组织病理学和免疫组织化学检测。UC引起显著的体重减轻、结肠重量增加和结肠重量长度比的变化。这些变化与炎症标志物升高和TXNIP/NLRP3通路标志物上调有关。在接受恩来汀、瑞舒伐他汀及其联合治疗后，所有测量参数均显著改善，其中联合治疗的疗效最显著。综上所述，本研究表明aa诱导UC与TXNIP/ nlrp3相关炎症标志物的表达增加有关，可能参与了该疾病的病理生理。恩格列素联合瑞舒伐他汀可下调TXNIP/ nlrp3相关的炎症信号，改善UC相关的生化和组织病理学改变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).