Phytochemical Profiling and Antioxidant Properties of Ziziphus lotus (L.) Fruits Supported by Xanthine Oxidase Inhibition and Molecular Docking

Ziziphus lotus (L.) Lam., an extremophyte shrub native to the Mediterranean basin, yields underexplored fruits as a source of therapeutic agents. This study combined in vitro and in silico approaches to evaluate the antioxidant potential of Z. lotus fruits and predict their potential to inhibit xanthine oxidase (XO), a key enzyme in reactive oxygen species generation and oxidative stress-related pathologies. The ethyl acetate extract from the hydroalcoholic macerate was enriched in total phenolics (281.33 ± 1.5 μg GAE/mg) and flavonoids (127.26 ± 5.89 μg RE/mg) and displayed remarkable effects against the ABTS•+ radical cation (IC50 = 18.49 ± 1.47 μg/mL) and phenanthroline reducing power (A0.5 = 8.38 ± 0.69 μg/mL), together with measurable xanthine oxidase inhibition (IC50 = 170.4 ± 5.90 μg/mL). The compounds tentatively identified by full-scan UHPLC-QtoF-HRMS were docked against XO (PDB ID: 3NVY), with phytosphingosine (−8.5 kcal/mol) and rutin (−8.3 kcal/mol) exhibiting the strongest binding affinities, forming favorable predicted interactions with critical catalytic residues, followed by 6‴-feruloylspinosin, 3′,5′-di-C-β-glucopyranosylphloretin and hexadecasphinganine (ranging from −7.8 to −7.6 kcal/mol). Predictive structure–activity relationships were also observed. These results provide insights into the antioxidant potential of Z. lotus phytochemicals and highlight the value of this extremophile plant as sustainable resource for phytotherapy and the management of oxidative stress-related diseases.