title: Myricetin inhibits the generation of superoxide anion by reduced form of xanthine oxidase.
abstract: Myricetin, a plant-derived flavonol, was found to inhibit the formation of uric acid in a mixed-type manner with IC50value of (8.66±0.03)×10-6molL-1and more potently inhibit the generation of superoxide anion (O2-) catalysed by xanthine oxidase (XOD) with IC50value of (4.55±0.02)×10-6molL-1. Inhibiting O2-generation by myricetin may be attributed to the reduced form of XOD with a substantially higher reduction potential for FADH/FADH2couple. Moreover, molecular docking verified that myricetin bound to the site around isoalloxazine ring in the flavin adenine dinucleotide (FAD) domain to block the diffusion of O2-out of the FAD site, resulting in the transfer of another electron from FADH2to O2-to form hydrogen peroxide. This study has provided new insight into the role of myricetin in inhibiting XOD catalysis, which may be beneficial to improve myricetin's potential application in functional foods.
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
authors.forename: Cen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China. Electronic address: gwzhang@ncu.edu.cn.
authors.forename: Guowen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Liao
authors.affiliation: School of Biological Sciences, The University of Auckland, Auckland 1142, New Zealand.
authors.forename: Deming
authors.initials: D
authors.lastname: Gong
mesh_terms: D002384:Catalysis; D005182:Flavin-Adenine Dinucleotide / Q000031:analogs & derivatives / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D062105:Molecular Docking Simulation; D010084:Oxidation-Reduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D013481:Superoxides; D005182:Flavin-Adenine Dinucleotide; C058805:1,5-dihydro-FAD; D014527:Uric Acid; C040015:myricetin; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase
keywords: Inhibition; Molecular simulation; Myricetin; Superoxide anion; Xanthine oxidase