A comparative study of flavonoid analogues on streptozotocin–nicotinamide induced diabetic rats: Quercetin as a potential antidiabetic agent acting via 11β-Hydroxysteroid dehydrogenase type 1 inhibition

• DOI: 10.1016/j.ejmech.2010.02.049
• Publication Date: 2010-03-02T04:49:17Z
• Authors: Mariana Torres-Pi...; Rolffy Ortiz-Andrade; Rafael Villalobos...; Narender Singh; Jose L. Medina-Fr...; Scott P. Webster; Margaret Binnie; Gabriel Navarrete...; Samuel Estrada-Soto
• Keywords: Blood Glucose; Models, Molecular; Niacinamide; 0303 health sciences; Databases, Factual; Molecular Conformation; Computational Biology; Lipids; Diabetes Mellitus, Experimental; Rats; 3. Good health; 03 medical and health sciences; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Animals; Humans; Hypoglycemic Agents; Quercetin; Software

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.