Therapeutic Potential of Beaucarnea recurvata Leaf Extract Against Ulcerative Colitis: Integrating Phytochemical Profiling, Network Pharmacology, and Experimental Validation.

Ulcerative colitis represents a chronic inflammatory bowel disease with limited therapeutic options due to inadequate efficacy and adverse effects of current treatments. This study investigated the therapeutic potential of Beaucarnea recurvata leaf extract (BRLE) against ulcerative colitis using integrated computational and experimental approaches to address the need for safer, multi-targeted interventions. Phytochemical profiling was performed using UPLC-ESI-MS/MS analysis. Network pharmacology and molecular docking predicted therapeutic targets and mechanisms. In vivo validation employed an acetic acid-induced ulcerative colitis rat model with BRLE treatment at 100, 200, and 400 mg/kg doses, evaluating clinical parameters, histopathology, oxidative stress markers, inflammatory cytokines, and protein expression. UPLC-ESI-MS/MS revealed diverse bioactive compounds including steroidal saponins, triterpenes, and flavonoids. Network pharmacology identified 24 hub targets, and molecular docking revealed strong binding affinities (-6.5 to -9.1 kcal/mol) between BRLE compounds and inflammatory proteins including EGFR, SRC, STAT3, and AKT1. BRLE at 200 mg/kg significantly improved disease activity, restored glutathione levels, reduced malondialdehyde, normalized IL-10 and TNF-α levels, downregulated EGFR, SRC, STAT3, and AKT1 expression, and enhanced mucosal healing with reduced inflammatory infiltration. BRLE demonstrates significant anti-inflammatory, antioxidant, and tissue-protection effects through multi-target mechanisms, representing a promising therapeutic intervention for ulcerative colitis treatment. Further studies in chronic models, pharmacokinetic assessments, and clinical trials are needed to support its translation into therapeutic use.