title: Curcumin inhibits advanced glycation end product-induced oxidative stress and inflammatory responses in endothelial cell damage via trapping methylglyoxal.
abstract: Methylglyoxal (MGO)-induced carbonyl stress and pro-inflammatory responses have been suggested to contribute to endothelial dysfunction. Curcumin (Cur), a polyphenolic compound from Curcuma longa L., may protect endothelial cells against carbonyl stress-induced damage by trapping dicarbonyl compounds such as MGO. However, Cur-MGO adducts have not been studied in depth to date and it remains to be known whether Cur-MGO adducts are able to attenuate endothelial damage by trapping MGO. In the present study, 1,2-diaminobenzene was reacted with MGO to ensure the reliability of the reaction system. Cur was demonstrated to trap MGO at a 1:1 ratio to form adducts 1, 2 and 3 within 720 min. The structures of these adducts were identified by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. The kinetic curves of Cur (10(-7), 10(-6) and 10(-5) M) were measured from 0-168 h by fluorescent intensity. Cur significantly inhibited the formation of advanced glycation end products (AGEs). The differences in oxidative damage and the levels of pro-inflammatory cytokines following MGO + HSA or Cur-MGO treatment were investigated in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to the Cur-MGO reaction adducts significantly reduced the intracellular ROS levels and improved cell viability compared with MGO alone. Furthermore, there was a significant reduction in the expression levels of transforming growth factor-β1 and intercellular adhesion molecule(-1) following treatment with Cur-MGO adducts compared with MGO alone. These results provide further evidence that the trapping of MGO by Cur inhibits the formation of AGEs. The current study indicates that the protective effect of Cur on carbonyl stress and pro-inflammatory responses in endothelial damage occurs via the trapping of MGO.
authors.affiliation: Department of Pharmacognosy, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China.
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Sun
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
authors.forename: Jun Fei
authors.initials: JF
authors.lastname: Gu
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
authors.forename: Xiao Bin
authors.initials: XB
authors.lastname: Tan
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
authors.forename: Chun Fei
authors.initials: CF
authors.lastname: Wang
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
authors.forename: Xiao Bin
authors.initials: XB
authors.lastname: Jia
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China.
authors.forename: Ji Ping
authors.initials: JP
authors.lastname: Liu
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1; D011765:Pyruvaldehyde; D003474:Curcumin