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Background Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) with limited therapeutic options. Nintedanib, a multi-targeted kinase inhibitor, has been confirmed to exert definite antifibrotic effects in pulmonary fibrosis, making it a potential candidate drug for the treatment of IBD-associated intestinal fibrosis.Methods A total of 48 C57BL/6 mice were randomly divided into four groups (7 mice per group): Group A (prednisolone, 2 μg/day), Group B (sulfasalazine, 300 μg/day), Group C (nintedanib, 20 μg/day) and Group D (normal saline as the control). Intestinal fibrosis was induced by intermittent administration of 2% DSS via drinking water for four cycles, followed by model evaluation. Five mice were randomly selected from each group for model assessment and then excluded, and the remaining mice were continuously administered with the corresponding drugs for 14 days. The evaluation indicators included clinical parameters (body weight, disease activity index [DAI]), colon morphology, serum cytokines (transforming growth factor- β [TGF-β], tumor necrosis factor-α [TNF-α]), collagen deposition and histological scores.Results Body weight recovery: Group C (nintedanib) achieved the optimal body weight gain (19.6±1.4%), which was superior to that of Group A (18.7±0.2%) and Group B (19.4±1.5%), while Group D had the poorest recovery (3.4±0.9%, P<0.001).Colon morphology: The colon length in Group C was significantly increased (5.06±0.02 cm), which was markedly longer than that in Group A (4.63±0.15 cm) and Group B (4.21±0.18 cm); the colon weight in Group C was significantly reduced (0.209±0.013 g vs 0.252±0.012 g in Group A and 0.256±0.015 g in Group B, P<0.05).Anti-inflammatory effect: Nintedanib significantly decreased the serum levels of TGF- β (30±2.5 pg/mL) and TNF-α (35±3.0 pg/mL), with the efficacy superior to that of conventional drugs (P<0.05). Antifibrotic effect: Masson’s trichrome staining showed that the collagen deposition in Group C (25±3.2%) was significantly lower than that in Group A (35±4.2%) and Group B (34±3.8%) (P<0.05), which was close to the reported standard level of antifibrosis (IDDF2026-ABS-0129 Figure 1. Nintedanib vs traditional drugs mechanism, IDDF2026-ABS-0129 Figure 2. Nintedanib efficacy in IBD fibrosis).Conclusions In the DSS-induced mouse model of intestinal fibrosis, nintedanib exerts significantly better therapeutic efficacy than conventional prednisolone and sulfasalazine, with stronger anti-inflammatory and antifibrotic effects. These findings support the repurposing of nintedanib as a potential therapeutic option for stricturing Crohn’s disease ( IDDF2026-ABS-0129 Figure 3. Representative images of colonic fibrosis by Masson and Sirius Red staining).Abstract IDDF2026-ABS-0129 Figure 1Abstract IDDF2026-ABS-0129 Figure 2Abstract IDDF2026-ABS-0129 Figure 3