title: Quercetin inhibits advanced glycation end product formation via chelating metal ions, trapping methylglyoxal, and trapping reactive oxygen species.
abstract: Physiological concentration of Mg2+, Cu2+, and Zn2+accelerated AGE formation only in glucose-mediated conditions, which was effectively inhibited by chelating ligands. Only quercetin (10) inhibited MGO-mediated AGE formation as well as glucose- and ribose-mediated AGE formation among 10 polyphenols (1-10) tested. We performed an additional structure-activity relationship (SAR) study on flavanols (10, 11, 12, 13, and 14). Morin (12) and kaempherol (14) showed inhibitory activity against MGO-mediated AGE formation, whereas rutin (11) and fisetin (13) did not. These observations indicate that 3,5,7,4'-tetrahydroxy and 4-keto groups of 10 are important to yield newly revised mono-MGO adducts (16 and 17) and di-MGO adduct (18) having cyclic hemiacetals, while 3'-hydroxy group is not essential. We propose here a comprehensive inhibitory mechanism of 10 against AGE formation including chelation effect, trapping of MGO, and trapping of reactive oxygen species (ROS), which leads to oxidative degradation of 18 to 3,4-dihydroxybenzoic acid (15) and other fragments.
authors.affiliation: a Division of Applied Bioscience, Graduate School of Agriculture , Hokkaido University , Sapporo , Japan.
authors.forename: Mohammad Nazrul Islam
authors.initials: MN
authors.lastname: Bhuiyan
authors.affiliation: a Division of Applied Bioscience, Graduate School of Agriculture , Hokkaido University , Sapporo , Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Mitsuhashi
authors.affiliation: a Division of Applied Bioscience, Graduate School of Agriculture , Hokkaido University , Sapporo , Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sigetomi
authors.affiliation: a Division of Applied Bioscience, Graduate School of Agriculture , Hokkaido University , Sapporo , Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ubukata
mesh_terms: D000818:Animals; D002417:Cattle; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D019216:Metals, Heavy / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011765:Pyruvaldehyde / Q000378:metabolism*; D011794:Quercetin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D002614:Chelating Agents; D017127:Glycation End Products, Advanced; D019216:Metals, Heavy; D017382:Reactive Oxygen Species; D011765:Pyruvaldehyde; D011794:Quercetin; D010100:Oxygen
keywords: advanced glycation end products (AGEs); chelation effect; hemiacetal form of di-MGO adduct; trapping MGO (methylglyoxal); trapping ROS (reactive oxygen species)