(+)-Catechin ameliorates diabetic nephropathy by trapping methylglyoxal in type 2 diabetic mice

Mol Nutr Food Res. 2014 Dec;58(12):2249-60. doi: 10.1002/mnfr.201400533. Epub 2014 Oct 27.

Abstract

Scope: 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.

Methods and 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.

Conclusion: 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.

Keywords: (+)-Catechin; Diabetic nephropathy; Inflammation; Methylglyoxal; db/db mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catechin / pharmacology*
  • Cell Line
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetic Nephropathies / drug therapy*
  • Disease Progression
  • Down-Regulation
  • Glycation End Products, Advanced / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Pyruvaldehyde / metabolism*
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Glycation End Products, Advanced
  • Interleukin-1beta
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Pyruvaldehyde
  • Catechin