Orange Peel Powder Improves Constipation-Related Phenotypes and Is Associated with Coordinated Colonic and...

This study aimed to determine whether orange peel powder (OP) improves constipation-related phenotypes in a doxorubicin- and loperamide-treated rat model and whether such improvement is accompanied by coordinated histological and molecular changes in colon and brain tissues.

Forty-eight 12-wk-old male Sprague-Dawley rats were randomly assigned to 6 groups (n = 8/group): blank control (BC), aging control (AG), aging constipation control (ACG), and low-, medium-, and high-dose OP groups (0.1575, 0.315, and 0.63 g/kg, respectively). An aging-like phenotype was induced by intraperitoneal doxorubicin (2 mg/kg) for 4 wk, followed by loperamide gavage (2 mg/kg) for 14 d. OP was then administered by gavage for 4 wk. Body weight, defecation frequency, fecal moisture content, and small-intestinal propulsion rate were assessed. Gastrointestinal hormones, inflammatory markers, and oxidative stress indices were measured in serum, colon tissue, and/or brain tissue, as appropriate. Colon and brain histology were examined by hematoxylin-eosin staining. Tight junction proteins (ZO-1, occludin, and claudin-1) and endocannabinoid system-related proteins (CB1, CB2, and FAAH) in colon and brain tissues were assessed by western blotting.

Compared with the BC group, the AG and ACG groups showed lower body weight gain and worse constipation-related phenotypes. The ACG group also exhibited a higher inflammatory and oxidative stress-related burden, altered gastrointestinal hormone profiles, histological abnormalities in the colon and brain, and lower expression of tight junction proteins in the colon and brain. OP intervention, particularly at the medium dose, improved defecation frequency, fecal moisture content, and small-intestinal propulsion rate; reduced interleukin-6, tumor necrosis factor-α, vasoactive intestinal peptide, and malondialdehyde; increased gastrin, motilin, and total superoxide dismutase activity; and upregulated ZO-1, occludin, and claudin-1 expression in the colon and brain.

OP improved constipation-related phenotypes in this composite model and was associated with coordinated systemic, colonic, and brain-related changes. These findings are descriptive and do not establish restoration of barrier function or a direct gut-brain mechanistic pathway.