Department of Pharmacy, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China.
Department of Rehabilitation Medicine, Wuhan Ninth Hospital, Wuhan, 430081, China.
Dig Dis Sci. 2024 Oct;69(10):3753-3759. doi: 10.1007/s10620-024-08618-z. Epub 2024 Sep 11.
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.
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.
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.
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.
溃疡性结肠炎（UC）是一种影响结肠的慢性炎症性疾病，其全球发病率正在上升。尽管患病率不断上升，但 UC 的有效治疗选择仍然有限。
我们利用 NF-κB 启动子双荧光报告系统筛选能够抑制 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。在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中进一步评估了其疗效。分析包括评估结肠病变、炎症标志物和信号通路激活，重点关注 NF-κB 和 Notch 信号通路。
拉西地平在报告系统中有效抑制了 p65 和 IκBα 的磷酸化。在 DSS 诱导的结肠炎小鼠模型中，拉西地平治疗导致结肠病变和炎症标志物减少。靶分析显示 Notch 信号通路显著富集。此外，拉西地平抑制 DSS 刺激的结肠中 NF-κB 和 Notch 的激活。
拉西地平在 UC 中表现出保护作用，可减轻炎症并调节关键信号通路。这些发现表明拉西地平可能是治疗 UC 的有前途的候选药物。
