Phytochemical Profiling, Biological Evaluation, and Molecular Insights Into the Urease Inhibitory Potential of...

Fraxinus angustifolia Vahl. has long been used in traditional medicine for the management of inflammatory and gastrointestinal disorders. This study investigated the anti-urease, anti-Helicobacter pylori, and anti-inflammatory activities of the ethanolic leaf extract and its phenolic fractions, with a focus on the mechanisms underlying these effects. The extracts exhibited inhibition of urease activity and bacterial growth, with the aqueous fraction of chloroform (AC) showing the most pronounced effect (urease IC₅₀ = 384.55 ± 4.31 µg/mL; MIC = 1000 µg/mL against H. pylori). HPLC-DAD analysis identified 11 phenolic compounds, including flavones and flavonols. Quercetin-3-O-glucoside (3585.25 µg/g) and rutin (936.11 µg/g), were the most abundant phenolic compounds in the crude extract (CE), whereas chlorogenic acid (824.51 µg/g), rosmarinic acid (586.47 µg/g), and apigenin (148.25 µg/g) predominated in the AC fraction. Enzyme kinetic analysis revealed a mixed mode of urease inhibition, while molecular docking predicted stable binding of phenolic compounds within the urease catalytic pocket and adjacent regions. These findings provide new evidence supporting F. angustifolia leaves as a relevant source of urease inhibitors, suggesting its potential for the management of H. pylori infection and related gastric disorders. Further studies are underway to isolate the active compounds and evaluate their in vivo efficacy.