title: Effect of Soy Sauce on Serum Uric Acid Levels in Hyperuricemic Rats and Identification of Flazin as a Potent Xanthine Oxidase Inhibitor.
abstract: This is the first report on the ability of soy sauce to effectively reduce the serum uric acid levels and xanthine oxidase (XOD) activities of hyperuricemic rats. Soy sauce was partitioned sequentially into ethyl acetate and water fractions. The ethyl acetate fraction with strong XOD inhibition effect was purified further. On the basis of xanthine oxidase inhibitory (XOI) activity-guided purification, nine compounds including 3,4-dihydroxy ethyl cinnamate, diisobutyl terephthalate, harman, daidzein, flazin, catechol, thymine, genistein, and uracil were obtained. It was the first time that 3,4-dihydroxy ethyl cinnamate and diisobutyl terephthalate had been identified from soy sauce. Flazin with hydroxymethyl furan ketone group at C-1 and carboxyl at C-3 exhibited the strongest XOI activity (IC50 = 0.51 ± 0.05 mM). According to fluorescence quenching and molecular docking experiments, flazin could enter into the catalytic center of XOD to interact with Lys1045, Gln1194, and Arg912 mainly by hydrophobic forces and hydrogen bonds. Flazin, catechol, and genistein not only were potent XOD inhibitors but also held certain antioxidant activities. According to ADME (absorption, distribution, metabolism, and excretion) simulation in silico, flazin had good oral bioavailability in vivo.
authors.affiliation: School of Food Science and Engineering, South China University of Technology , Guangzhou 510640, China.|Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center , Guangzhou 510640, China.
authors.forename: Huipin
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Food Science and Engineering, South China University of Technology , Guangzhou 510640, China.|Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center , Guangzhou 510640, China.|State Key Laboratory of Pulp and Paper Engineering, South China University of Technology , Guangzhou 510640, China.
authors.forename: Mouming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: School of Food Science and Engineering, South China University of Technology , Guangzhou 510640, China.|Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center , Guangzhou 510640, China.
authors.forename: Guowan
authors.initials: G
authors.lastname: Su
authors.affiliation: School of Food Science and Engineering, South China University of Technology , Guangzhou 510640, China.|Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center , Guangzhou 510640, China.
authors.forename: Lianzhu
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Food Science and Engineering, Jinan University , Guangzhou 510632, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002243:Carbolines / Q000493:pharmacokinetics / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005663:Furans / Q000493:pharmacokinetics / Q000494:pharmacology*; D033461:Hyperuricemia / Q000139:chemically induced / Q000178:diet therapy* / Q000188:drug therapy; D008297:Male; D062105:Molecular Docking Simulation; D010094:Oxonic Acid / Q000009:adverse effects; D017207:Rats, Sprague-Dawley; D045730:Soy Foods / Q000032:analysis; D014527:Uric Acid / Q000097:blood*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D002243:Carbolines; D004791:Enzyme Inhibitors; D005663:Furans; C055780:flazin; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid; D014969:Xanthine Oxidase
keywords: flazin; hyperuricemia; soy sauce; xanthine oxidase; xanthine oxidase inhibitory activity