Citrus unshiu Peel Extract Enhances Barrier Integrity and Modulates Inflammation and Microbiota in DSS-Induced Colitis

Abstract

Inflammatory bowel disease, including ulcerative colitis, is a chronic disorder characterized by inflammation, impaired intestinal barrier function, and gut microbiota imbalance. Citrus fruits, particularly their peels, are rich in bioactive flavonoids such as narirutin and hesperidin, which possess anti-inflammatory properties. However, citrus peels are often discarded and wasted during juice processing, presenting a missed opportunity for therapeutic use. This study aims to compare the therapeutic potential of Citrus unshiu peel (CPE) and pulp (CPU) extracts in a mouse model of dextran sulfate sodium (DSS)–induced colitis. Six-week-old male BALB/c mice were divided into nine groups, including controls and treatment groups receiving CPE or CPU at varying doses (50, 100, and 200 mg/kg). Colitis was induced using 3% DSS for 14 days. Results showed that CPE at 200 mg/kg significantly improved colitis symptoms: It reduced body weight loss, spleen enlargement, and disease activity index scores. CPE treatment was associated with the enhancement of intestinal barrier function, which was evidenced by the upregulation of occludin and claudin levels. CPE also favorably modulated gut microbiota diversity, increasing beneficial species such as Akkermansia muciniphila and Bacteroides acidifaciens. CPE contained higher levels of narirutin and hesperidin compared to CPU, correlating with its more pronounced therapeutic effects. These findings suggest that CPE could serve as a valuable functional ingredient for colitis management, addressing both health and environmental concerns.