Quercetin alleviates ulcerative colitis through inhibiting CXCL8-CXCR1/2 axis: a network and transcriptome analysis.

Area of Science:

• Gastroenterology and Immunology
• Pharmacology and Natural Products

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by intestinal damage.
• Mucosal healing is a key indicator of therapeutic success in UC.
• Quercetin, a natural flavonoid, possesses anti-inflammatory and antioxidant properties.

Purpose of the Study:

• To investigate the therapeutic potential of quercetin in a murine model of ulcerative colitis (UC).
• To elucidate the underlying molecular mechanisms of quercetin's action in UC.

Main Methods:

• Integrated network predictions and transcriptomic analyses to identify quercetin targets in UC.
• Utilized a dextran sulfate sodium (DSS)-induced mouse model of UC.
• Assessed pathological morphology, inflammatory markers, and mucosal barrier proteins.

Main Results:

• Network analysis identified the CXCL8-CXCR1/2 axis as a key target in UC.
• Quercetin treatment ameliorated DSS-induced colitis symptoms, restoring colonic architecture and reducing inflammation.
• Quercetin enhanced intestinal barrier integrity by increasing tight junction protein expression and decreasing inflammatory mediators (IL-17A, NF-κB, CXCL8, CXCR1, CXCR2).

Conclusions:

• Quercetin demonstrates significant therapeutic effects in a murine model of UC.
• Inhibition of the CXCL8-CXCR1/2 signaling pathway is a key mechanism underlying quercetin's efficacy.
• These findings support the clinical application and pharmaceutical development of quercetin for UC treatment.