title: Natural compounds containing a catechol group enhance the formation of Nε-(carboxymethyl)lysine of the Maillard reaction.
abstract: Inhibition of advanced glycation end-product (AGE) formation is a potential strategy for the prevention of clinical diabetes complications. Screening for new AGE inhibitors revealed several natural compounds that inhibited the formation of N(ε)-(carboxymethyl)lysine (CML), a major antigenic AGE structure, whereas natural compounds containing a catechol group, such as gallic acid and epicatechin, significantly enhanced CML formation. A similar enhancing effect was also observed by culturing THP-1 macrophages in the presence of catechol compounds. Although 4-methylcatechol significantly enhanced CML formation from glycated HSA (gHSA), a model for Amadori proteins, analogues of catechol such as 5-methylresorcinol and methylhydroquinone showed no enhancing effect. Even though 1mM 4-methylcatechol, epicatechin, and gallic acid significantly enhanced CML formation from gHSA, it was significantly inhibited by decreasing their concentration. The enhancing effect of 1mM catechol compounds was inhibited in the presence of the glutathione peroxidase system, thus demonstrating that hydrogen peroxide generated from catechol compounds plays an important role in the enhancement of CML formation. Furthermore, administration of 500mg/kg/day epicatechin to STZ-induced diabetic mice for 45days enhanced CML accumulation at the surface area of gastric epithelial cells in the stomach. This study provides the first evidence that high amounts of catechol-containing structures enhance oxidative stress, thus leading to enhanced CML formation, and this phenomenon may explain the paradoxical effect that some flavonoids have on redox status.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Naoko
authors.initials: N
authors.lastname: Kiyota
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Tsurushima
authors.forename: Makiko
authors.initials: M
authors.lastname: Yoshitomi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Mera
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakashita
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Araki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nohara
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism; D015416:Maillard Reaction / Q000187:drug effects*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013311:Streptozocin / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D002396:Catechols; D005609:Free Radicals; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D013311:Streptozocin; C048496:N(6)-carboxymethyllysine; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D008239:Lysine