拉西地平抑制NF-κB和Notch通路并减轻DSS诱导的结肠炎

IF 2.5 4区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Xuezhao Yu, Cheng Li, Yu Tao, Tingting Xia, Zhenyu Jia
{"title":"拉西地平抑制NF-κB和Notch通路并减轻DSS诱导的结肠炎","authors":"Xuezhao Yu, Cheng Li, Yu Tao, Tingting Xia, Zhenyu Jia","doi":"10.1007/s10620-024-08618-z","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, with a global incidence that is rising. Despite the increasing prevalence, effective treatment options for UC remain limited.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We utilized an NF-κB promoter dual fluorescence reporter system to screen for compounds that could inhibit p65 and IκBα phosphorylation. The anti-hypertension drug lacidipine was identified as a candidate. Its efficacy was further evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. The analysis included the assessment of colon lesions, inflammation markers, and signal pathway activation, with a focus on NF-κB and Notch signaling.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Lacidipine effectively inhibited p65 and IκBα phosphorylation in the reporter system. In the DSS-induced colitis murine model, lacidipine treatment led to a reduction in colon lesions and inflammatory markers. Target analysis showed significant enrichment of the Notch signaling pathway. Additionally, lacidipine inhibited both NF-κB and Notch activation in DSS-stimulated colons.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Lacidipine demonstrated a protective effect in UC, reducing inflammation and modulating key signaling pathways. These findings suggest that lacidipine could be a promising candidate for the treatment of UC.</p>","PeriodicalId":11378,"journal":{"name":"Digestive Diseases and Sciences","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lacidipine Inhibits NF-κB and Notch Pathways and Mitigates DSS-Induced Colitis\",\"authors\":\"Xuezhao Yu, Cheng Li, Yu Tao, Tingting Xia, Zhenyu Jia\",\"doi\":\"10.1007/s10620-024-08618-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, with a global incidence that is rising. Despite the increasing prevalence, effective treatment options for UC remain limited.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>We utilized an NF-κB promoter dual fluorescence reporter system to screen for compounds that could inhibit p65 and IκBα phosphorylation. The anti-hypertension drug lacidipine was identified as a candidate. Its efficacy was further evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. The analysis included the assessment of colon lesions, inflammation markers, and signal pathway activation, with a focus on NF-κB and Notch signaling.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>Lacidipine effectively inhibited p65 and IκBα phosphorylation in the reporter system. In the DSS-induced colitis murine model, lacidipine treatment led to a reduction in colon lesions and inflammatory markers. Target analysis showed significant enrichment of the Notch signaling pathway. Additionally, lacidipine inhibited both NF-κB and Notch activation in DSS-stimulated colons.</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusion</h3><p>Lacidipine demonstrated a protective effect in UC, reducing inflammation and modulating key signaling pathways. These findings suggest that lacidipine could be a promising candidate for the treatment of UC.</p>\",\"PeriodicalId\":11378,\"journal\":{\"name\":\"Digestive Diseases and Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Digestive Diseases and Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10620-024-08618-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Digestive Diseases and Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10620-024-08618-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景溃疡性结肠炎(UC)是一种影响结肠的慢性炎症,全球发病率呈上升趋势。我们利用 NF-κB 启动子双荧光报告系统筛选可抑制 p65 和 IκBα 磷酸化的化合物。抗高血压药物拉西地平被确定为候选药物。在右旋糖酐硫酸钠(DSS)诱导的小鼠结肠炎模型中对其疗效进行了进一步评估。分析包括结肠病变、炎症标志物和信号通路激活的评估,重点是 NF-κB 和 Notch 信号转导。在 DSS 诱导的小鼠结肠炎模型中,拉西地平治疗可减少结肠病变和炎症标志物。靶点分析表明,Notch 信号通路明显富集。结论 拉西地平对 UC 具有保护作用,能减轻炎症反应并调节关键信号通路。这些研究结果表明,拉西地平有望成为治疗 UC 的候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Lacidipine Inhibits NF-κB and Notch Pathways and Mitigates DSS-Induced Colitis

Lacidipine Inhibits NF-κB and Notch Pathways and Mitigates DSS-Induced Colitis

Background

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, with a global incidence that is rising. Despite the increasing prevalence, effective treatment options for UC remain limited.

Methods

We utilized an NF-κB promoter dual fluorescence reporter system to screen for compounds that could inhibit p65 and IκBα phosphorylation. The anti-hypertension drug lacidipine was identified as a candidate. Its efficacy was further evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. The analysis included the assessment of colon lesions, inflammation markers, and signal pathway activation, with a focus on NF-κB and Notch signaling.

Results

Lacidipine effectively inhibited p65 and IκBα phosphorylation in the reporter system. In the DSS-induced colitis murine model, lacidipine treatment led to a reduction in colon lesions and inflammatory markers. Target analysis showed significant enrichment of the Notch signaling pathway. Additionally, lacidipine inhibited both NF-κB and Notch activation in DSS-stimulated colons.

Conclusion

Lacidipine demonstrated a protective effect in UC, reducing inflammation and modulating key signaling pathways. These findings suggest that lacidipine could be a promising candidate for the treatment of UC.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Digestive Diseases and Sciences
Digestive Diseases and Sciences 医学-胃肠肝病学
CiteScore
6.40
自引率
3.20%
发文量
420
审稿时长
1 months
期刊介绍: Digestive Diseases and Sciences publishes high-quality, peer-reviewed, original papers addressing aspects of basic/translational and clinical research in gastroenterology, hepatology, and related fields. This well-illustrated journal features comprehensive coverage of basic pathophysiology, new technological advances, and clinical breakthroughs; insights from prominent academicians and practitioners concerning new scientific developments and practical medical issues; and discussions focusing on the latest changes in local and worldwide social, economic, and governmental policies that affect the delivery of care within the disciplines of gastroenterology and hepatology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信