Therapeutic effect of the sulforaphane derivative JY4 on ulcerative colitis through the NF-κB-p65 pathway.

Autor: Zhao XJ; 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., Zhang YR; Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, 300020, Tianjin, P. R. of China., Bai WF; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, 163316, Daqing, P. R. of China., Sun TY; High-Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, 300457, Tianjin, P. R. of China., Yang YF; High-Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, 300457, Tianjin, P. R. of China.; College of Pharmacy, Nankai University, 300350, Tianjin, P. R. of China., Wang TX; High-Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, 300457, Tianjin, P. R. of China.; College of Pharmacy, Nankai University, 300350, Tianjin, P. R. of China., Bai CG; High-Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of BioMedicine, 300457, Tianjin, P. R. of China. baicuigai@tjab.org.
Jazyk: angličtina
Zdroj: Inflammopharmacology [Inflammopharmacology] 2022 Oct; Vol. 30 (5), pp. 1717-1728. Date of Electronic Publication: 2022 Aug 09.
DOI: 10.1007/s10787-022-01044-5
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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