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

Area of Science:

• * Pharmacology
• * Gastroenterology
• * Immunology

Background:

• * Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
• * Dextran sodium sulfate (DSS) is commonly used to induce experimental models of UC in rodents.
• * The NF-κB signaling pathway plays a critical role in UC pathogenesis.

Purpose of the Study:

• * To evaluate the therapeutic efficacy of JY4, a sulforaphane derivative, in mouse models of UC.
• * To investigate the mechanism of action of JY4, specifically its effect on the NF-κB pathway.
• * To assess the oral bioavailability of JY4.

Main Methods:

• * Acute and chronic ulcerative colitis were induced in mice using DSS.
• * JY4 was administered orally, and its effects on clinical symptoms and colonic tissue were assessed.
• * Oral bioavailability of JY4 was determined by comparing oral and intravenous administration.
• * Molecular mechanisms were explored using dual-luciferase reporter assays, immunofluorescence, Western blot, and immunohistochemistry.

Main Results:

• * Oral JY4 significantly ameliorated UC symptoms, including body weight loss, diarrhea, and bloody stools.
• * Histological analysis revealed reduced colonic ulceration and inflammatory cell infiltration in JY4-treated mice.
• * JY4 demonstrated an oral bioavailability of 5.67%, suggesting adequate intestinal absorption.
• * Mechanistically, JY4 was found to inhibit the NF-κB-p65 signaling pathway, reducing downstream inflammatory mediators.

Conclusions:

• * JY4 exhibits significant anti-inflammatory and therapeutic effects in experimental models of ulcerative colitis.
• * Inhibition of the NF-κB pathway is a key mechanism underlying JY4's efficacy.
• * JY4 represents a promising novel therapeutic candidate for ulcerative colitis treatment.