title: (+)-Catechin ameliorates diabetic nephropathy by trapping methylglyoxal in type 2 diabetic mice.
abstract: METHODS
  Accumulation of glycolytic metabolite methylglyoxal (MG) in diabetic kidney is thought to contribute to the pathogenesis of nephropathy, either as a direct toxin or as a precursor for advanced glycation end products (AGEs). Using (+)-catechin (CE), a novel MG trapper, we investigated whether MG trapping is sufficient to prevent the progression of diabetic nephropathy in type 2 diabetic mice.
  
  
  RESULTS
  CE markedly trapped exogenous MG in a time- and dose-dependent manner and formed mono-MG-CE and di-MG-CE adducts, which were characterized by HPLC-ESI-Q-TOFMS. In vivo, CE administration for 16 wk significantly ameliorated renal dysfunction in type 2 diabetic db/db mice, partially due to MG trapping, which in turn inhibited AGEs formation and lowered proinflammatory cytokines, including tumor necrosis factor α and IL-1β. Similarly, the MG trapping and cellular signaling inhibition effects of CE were observed in human endothelium-derived cells under high glucose conditions.
  
  
  CONCLUSIONS
  CE might ameliorate renal dysfunction in diabetic mice as consequences of inhibiting AGEs formation and cutting off inflammatory pathway via MG trapping. Thus, CE may be a potential natural product as an MG scavenger against diabetes-related complications.
authors.affiliation: State Key Laboratory of Earth Surface Processes and Resource Ecology, Beijing Normal University, Beijing, P. R. China; Beijing Area Major Laboratory of Protection and Utilization of Chinese Medicine Resources, Beijing Normal University, Beijing, P. R. China; Engineering Research Center of Natural Medicine, Ministry of Education, Beijing Normal University, Beijing, P. R. China.
authors.forename: Dina
authors.initials: D
authors.lastname: Zhu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Qile
authors.initials: Q
authors.lastname: Zhou
authors.forename: Shijun
authors.initials: S
authors.lastname: Yan
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Sheng
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002392:Catechin / Q000494:pharmacology*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D018450:Disease Progression; D015536:Down-Regulation; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D011765:Pyruvaldehyde / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D053583:Interleukin-1beta; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D011765:Pyruvaldehyde; D002392:Catechin
keywords: (+)-Catechin; Diabetic nephropathy; Inflammation; Methylglyoxal; db/db mice