Phytochemical and Computational Discovery of Potent Xanthine Oxidase Inhibitors From Ziziphus lotus L. Leaves and Seeds

ABSTRACT Ziziphus lotus (L.), traditionally recognised for its anti‐inflammatory and antioxidant properties, has received limited scientific exploration regarding its potential as an antigout agent. This study provides the first investigation of the inhibitory capacity of Z. lotus seed and leaf extracts against bovine xanthine oxidase (BXO), a key enzyme in uric acid biosynthesis and the pathogenesis of gout. To characterise its bioactive constituents, the potent extract was subjected to liquid chromatography–high‐resolution electrospray ionisation mass spectrometry (LC–HRESIMS)‐based phytochemical profiling. In vitro evaluation confirmed potent inhibitory effects, with the seed extract (IC 50 = 40.63 ± 0.41 µg/mL) showing superior activity over the leaf extract (IC 50 = 61.06 ± 1.15 µg/mL). LC–HRESIMS profiling of the seed extract identified fourteen metabolites, dominated by syringic acid (16 240.00 µg/g extract), sinapinic acid (3688.80 µg/g extract), and rutin (1918.00 µg/g extract) as the major constituents. A computational study focused on phytochemicals not previously assessed against XO; molecular docking demonstrated strong binding interactions to the target protein, suggesting promising inhibitory potential. ADMET and drug‐likeness assessments highlighted (+)‐ trans taxifolin as the most promising candidate for drug development. Overall, these findings establish Z. lotus seeds as a valuable source of natural xanthine oxidase inhibitors and underscore their potential as novel phytotherapeutic agents for treating gout and hyperuricemia.