High-Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, 300457, Tianjin, P. R. of China.
Tianjin Jena Pharmaceutical Technology Development Co., LTD, 300000, Tianjin, P. R. of China.
Inflammopharmacology. 2022 Oct;30(5):1717-1728. doi: 10.1007/s10787-022-01044-5. Epub 2022 Aug 9.
The efficacy of the sulforaphane derivative JY4 was evaluated in acute and chronic mouse models of ulcerative colitis induced by dextran sodium sulfate. Oral administration of JY4 led to significant improvements in symptoms, with recovery of body weight and colorectal length, together with reduced diarrhoea, bloody stools, ulceration of colonic tissue and infiltration of inflammatory cells. The oral bioavailability of JY4, determined by comparing oral dosing with injection into the tail vein, was 5.67%, which was comply with the idea in the intestinal function. Using a dual-luciferase reporter assay, immunofluorescence studies, western blot analysis and immunohistochemical staining, JY4 was shown to significant interfere with the NF-κB-p65 signaling pathway. By preventing the activation of NF-κB-p65, JY4 inhibited the overexpression of downstream inflammatory factors, thereby exerting an anti-inflammatory effect on the intestinal tract. This study thus provides a promising candidate drug, and a new concept for the treatment of ulcerative colitis.
硫代葡萄糖苷 JY4 的疗效在葡聚糖硫酸钠诱导的急性和慢性溃疡性结肠炎小鼠模型中进行了评估。JY4 的口服给药导致症状显著改善,体重和结肠长度恢复,同时减少腹泻、血性粪便、结肠组织溃疡和炎症细胞浸润。通过比较尾静脉注射和口服给药,测定 JY4 的口服生物利用度为 5.67%,这符合肠道功能的理念。通过双荧光素酶报告基因检测、免疫荧光研究、Western blot 分析和免疫组织化学染色,JY4 显著干扰 NF-κB-p65 信号通路。通过阻止 NF-κB-p65 的激活,JY4 抑制下游炎症因子的过度表达,从而对肠道发挥抗炎作用。因此,本研究为溃疡性结肠炎的治疗提供了一种有前景的候选药物和新的概念。