10th U6+ Consortium of African Universities International Conference

Cannabis sativa has long been used ethnomedicinally for inflammation-related conditions, but the phytocompounds responsible for COX-2 and lipoxygenase inhibition remain poorly characterized. This study integrated virtual screening against COX-2 (3Q7D), 15-LOX (4NRE), and 5-LOX (6N2W), and rat paw edema models to identify anti-inflammatory leads. Dried C. sativa leaves were sequentially extracted (methanol, then water; 300 g, 2.5 L, 72 h). Adult albino rats (n=6/group) were orally pre-treated with methanol or aqueous extract (100–400 mg/kg), diclofenac (10 mg/kg, positive control), or saline (10 mL/kg, negative control) before carrageenan or formalin-induced paw edema; paw thickness was recorded over 180 min. Twenty GC-MS phytocompounds plus diclofenac, meloxicam, and NDGA were docked against the three receptors in PyRx (Chimera prep; Open Babel ligand prep; Discovery Studio/PyMOL/LIGPLOT post-docking analysis). Results: Both extracts significantly reduced paw edema (p<0.05). In carrageenan-induced edema, methanol extract (400 mg/kg) reduced paw thickness by 25.51% at 90 min, while aqueous extract (400 mg/kg) sustained inhibition through 180 min (18.13%; p<0.05). In formalin-induced edema, aqueous extract produced significant inhibition at 200 mg/kg (20.32%) and 400 mg/kg (18.48%), whereas methanol extract was significant only at 400 mg/kg (9.97%; p<0.05). Multi-receptor docking identified isoaromadendrene epoxide as the top-ranked compound, with binding affinities of −10.4, −9.3, and −10.5 kcal/mol against COX-2, 15-LOX, and 5-LOX, respectively, outperforming reference drugs. Cannabinol ranked second against COX-2 (−8.9 kcal/mol versus diclofenac −6.9 kcal/mol) and shared a CYS 47(A) active-site interaction, highlighting both compounds as promising multi-target anti-inflammatory candidates for further investigation.