A comparative study of flavonoid analogues on streptozotocin-nicotinamide induced diabetic rats: quercetin as a potential antidiabetic agent acting via 11beta-hydroxysteroid dehydrogenase type 1 inhibition

Eur J Med Chem. 2010 Jun;45(6):2606-12. doi: 10.1016/j.ejmech.2010.02.049. Epub 2010 Mar 1.

Abstract

The aim of the current study was to investigate the oral antidiabetic activity of six structurally related flavonoids: flavone (1), 3-hydroxyflavone (2), 6-hydroxyflavone (3), 7-hydroxyflavone (4), chrysin (5) and quercetin (6). Normoglycemic and STZ-nicotinamide diabetic rats were treated with these flavonoids (50 mg/kg) and the hypoglycemic and antidiabetic effects in acute and sub acute (five days of treatment) experiments were determined. Compounds 1, 5 and 6 were found most active in both experiments in comparison with control group (p<0.05). After five days of administration to STZ-nicotinamide diabetic rats, flavonoids induced a significantly diminishing of total cholesterol, TG and LDL and an augment of HDL compared with the control group (p<0.05). The in vitro inhibitory activity of the compounds against 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) was also evaluated. Quercetin, the most active compound, was docked into the crystal structure of 11beta-HSD1. Docking results indicate potential hydrogen bond interactions with hydroxyl groups of catalytic amino acid residues.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / chemistry
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Computational Biology
  • Databases, Factual
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / enzymology*
  • Diabetes Mellitus, Experimental / metabolism
  • Humans
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Lipids / blood
  • Models, Molecular
  • Molecular Conformation
  • Niacinamide / pharmacology*
  • Quercetin / analogs & derivatives*
  • Quercetin / chemistry
  • Quercetin / metabolism
  • Quercetin / pharmacology*
  • Rats
  • Software

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Lipids
  • Niacinamide
  • Quercetin
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1