Scopoletin Mitigates DSS-Induced Ulcerative Colitis by Attenuating NF-κB/MMP-9 Mediated Inflammation and Activating the Nrf2 Pathway to Preserve Colonic Barrier Integrity

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, characterized by persistent mucosal inflammation and epithelial barrier disruption. This study investigated the therapeutic efficacy of Scopoletin, a natural coumarin derivative with established anti-inflammatory and antioxidant properties, in a DSS-induced colitis model in Balb/c mice. A total of five experimental groups were established: a normal control, a DSS+ vehicle group, two Scopoletin-treated groups (10 and 30 mg/kg), and a reference group treated with Sulfasalazine (200 mg/kg). Network pharmacology analyses identified key inflammatory and immune-regulatory pathways potentially modulated by Scopoletin. In vivo assessments encompassed body weight monitoring, DAI scoring, colon length measurement, and histopathological evaluation using H&E, PAS, and Alcian blue staining. Scopoletin (30 mg/kg) treatment significantly ameliorated clinical and histological manifestations of colitis, including body weight loss and colonic shortening. Mechanistically, Scopoletin (30 mg/kg) attenuated the expression of pro-inflammatory cytokines such as TNF-α and IL-1β, suppressed NF-κB activation, MMP-9, COX-2 and enhanced the Nrf2 expression, leading to upregulation of antioxidant enzymes HO-1 and NQO1. Notably, Scopoletin (30 mg/kg) restored the expression of tight junction proteins such as Occludin and ZO-1, indicating reinforcement of epithelial barrier integrity. These findings demonstrated that Scopoletin protects against UC by suppressing inflammation, enhancing antioxidant defenses, and preserving mucosal barrier integrity, highlighting its potential as a therapeutic candidate for UC.