Hesperetin acts as a potent xanthine oxidase inhibitor: New evidence from its reactive oxygen suppression and enzyme binding

文献类型： 外文期刊

第一作者： Liu, Yinying

作者： Liu, Yinying;Lu, Hanyu;Lu, Shengmin;Liu, Yinying;Lu, Hanyu;Fang, Zhongxiang

作者机构：

关键词： Hesperetin; Xanthine oxidase; Interaction mechanism

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2025 年 306 卷

页码：

收录情况： SCI

摘要： Xanthine oxidase (XO) plays a crucial role in purine metabolism, catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid. Elevated uric acid levels can lead to hyperuricemia, a condition linked to gout, kidney stones, and other chronic diseases. Inhibiting XO activity represents a promising strategy for managing hyperuricemia. This study investigated the inhibitory effects of the flavonoid hesperetin enriched in citrus fruits on XO activity, its antioxidant properties against reactive oxygen species (ROS) generated by the XO reaction, and the underlying mechanisms of enzyme inhibition. Enzyme kinetics and spectroscopy revealed that hesperetin competitively inhibited XO at an inhibition constant of (2.15 +/- 0.05) x 10-6 mol/L through its binding to the molybdopterin active center of XO, preventing the entry of xanthine and the transfer of electrons, effectively scavenging superoxide radicals by inhibiting uric acid production and oxygen reduction, and inducing conformational changes in XO's structure. Fluorescence quenching indicated that hesperetin interacted with XO through a combination of static and dynamic quenching mechanisms. Molecular docking simulations demonstrated that hesperetin binded tightly to XO's active site, blocking substrate entry. Molecular dynamics confirmed that hesperetin stabilized the XO-hesperetin complex through reinforced hydrophobic and hydrogen-bond interactions. The results suggest that hesperetin can act as a potent natural xanthine oxidase inhibitor or a functional food supplement to alleviate hyperuricemia.

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