title: Identification and mode of action of 5-hydroxymethyl-2-furfural (5-hmf) and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA) as potent xanthine oxidase inhibitors in vinegars.
abstract: Vinegars have been used as an alternative remedy for treating gout, but the scientific basis remains to be elucidated. In this study, seven commercial vinegars and one laboratory-prepared red-koji vinegar were evaluated for the inhibitory activity of xanthine oxidase (XO), a critical enzyme catalyzing uric acid formation. Red-koji vinegar exhibited potent xanthine oxidase inhibitory (XOI) activity and was used for isolating active compounds. The substances under two peaks with XOI activity from HPLC were identified as 5-hydroxymethyl-2-furfural (5-HMF) and 1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (MTCA), by LC-MS-MS and NMR. The XO half-maximal inhibitory concentrations (IC(50)) of 5-HMF and MTCA were 168 and 860 μg/mL, respectively. In further mode-of-action analysis, the inhibitory mechanism of each compound was elucidated at the IC(50) level in the presence of various concentrations of xanthine as the substrate. The following Michaelis-Menten kinetics analysis of XO inhibition revealed uncompetitive and competitive patterns for 5-HMF and MTCA, respectively.
authors.affiliation: Department of Food Science, National Chiayi University , Chiayi 60004, Taiwan.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Lin
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Wu
authors.forename: Chien
authors.initials: C
authors.lastname: Su
authors.forename: Sophia
authors.initials: S
authors.lastname: Ferng
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Lo
authors.forename: Robin Y-Y
authors.initials: RY
authors.lastname: Chiou
mesh_terms: D019342:Acetic Acid / Q000737:chemistry*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D014969:Xanthine Oxidase / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D002243:Carbolines; D004791:Enzyme Inhibitors; C038114:1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D014969:Xanthine Oxidase; D019342:Acetic Acid