Trapping mechanism by di-d-psicose anhydride with methylglyoxal for prevention of diabetic nephropathy

Carbohydr Res. 2024 Jun:540:109125. doi: 10.1016/j.carres.2024.109125. Epub 2024 Apr 26.

Abstract

Di-d-psicose anhydride (DPA), derived from functional rare saccharide as d-psicose, is investigated for its strong chelating ability. Methylglyoxal (MGO), an important precursor of advanced glycation end-products (AGEs), promotes obesity, and causes complications such as diabetic nephropathy. On mesangial cells, DPA can substantially reduce the negative effects of MGO. DPA effectively trapping MGO in mesangial cells. The bonding properties of the DPA-MGO adduct were discussed by mass spectrometry and nuclear magnetic resonance (NMR). The NMR spectra of the DPA-MGO adduct provide evidence for chelation bonding. The inhibition of AGE formation and the mass spectrometry results of the DPA-MGO adduct indicate that DPA can scavenge MGO at a molar ratio of 1:1. DPA suppressed 330 % of the up-regulated receptor for an AGEs protein expression to a normal level and restored the suppressed glyoxalase 1 level to 86 % of the normal group. This research provides important evidence and theoretical basis for the development of AGE inhibitors derived from rare saccharide.

Keywords: Advanced glycation end-products; Di-d-psicose anhydride; Diabetic nephropathy; Methylglyoxal; d-Psicose.

MeSH terms

  • Anhydrides / chemistry
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / metabolism
  • Diabetic Nephropathies* / prevention & control
  • Glycation End Products, Advanced* / antagonists & inhibitors
  • Glycation End Products, Advanced* / metabolism
  • Humans
  • Lactoylglutathione Lyase / antagonists & inhibitors
  • Lactoylglutathione Lyase / metabolism
  • Mesangial Cells / drug effects
  • Mesangial Cells / metabolism
  • Pyruvaldehyde* / chemistry
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors
  • Receptor for Advanced Glycation End Products / metabolism

Substances

  • Pyruvaldehyde
  • Glycation End Products, Advanced
  • Lactoylglutathione Lyase
  • Receptor for Advanced Glycation End Products
  • Anhydrides
  • Chelating Agents