A novel enema formulation containing cannabidiol and sodium propionate for ulcerative colitis: preclinical assessment in a murine model

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, epithelial barrier disruption, and immune dysregulation. Cannabidiol (CBD), a non-psychoactive phytocannabinoid, and sodium propionate (Na-P), a short-chain fatty acid, posses complementary anti-inflammatory and epithelial-protective properties. This study aimed to evaluate the safety and efficacy of a novel rectal enema formulation combining CBD and Na-P in a murine model of dextran sodium sulfate (DSS)-induced colitis. Experimental colitis was induced in C57BL/6 mice via 2.5% DSS administration for five days. Mice received one of 4 daily rectal treatments from day 4 to day 11: saline, hyaluronic acid (HA, vehicle), HA + CBD, HA + Na-P, or HA + CBD+Na-P. Clinical disease activity was monitored through the Disease Activity Index (DAI), body weight, colon length, and histopathological evaluation. Colon length analysis demonstrated a 34.7% increase in length in the combination group versus saline control, significantly exceeding improvements observed with CBD or Na-P alone (p < 0.001). The combination treatment of CBD and Na-P led to a significant and sustained reduction in DAI scores compared to controls and monotherapies. Notably, the combination group exhibited a steeper improvement in DAI from day 6 onwards and showed superior outcomes on day 11 (p < 0.004 vs. HA). Body weight loss was markedly attenuated in the combination group, with statistical significance observed from day 6 (p < 0.05), while single-agent treatments exhibited only partial benefit. Histopathological scores were reduced in the combination group, accompanied by decreased neutrophilic infiltration and attenuation of mucosal damage, though statistical significance was not reached compared to monotherapies. Importantly, no hemorrhages or fibrin deposits were observed in any group, supporting the safety profile of the combination treatment. This preclinical study demonstrates that rectal administration of a CBD and Na-P enema exerts potential synergistic therapeutic effects in experimental UC, effectively reducing disease severity, preserving colon morphology, and mitigating histopathological damage. These findings support further clinical investigation of this novel dual-targeted approach for UC management.