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

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 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) was also evaluated. Quercetin, the most active compound, was docked into the crystal structure of 11β-HSD1. Docking results indicate potential hydrogen bond interactions with hydroxyl groups of catalytic amino acid residues.

Graphical abstractNormoglycemic and STZ-nicotinamide induced diabetic rats were treated with flavone (1), 3-hydroxyflavone (2), 6-hydroxyflavone (3), 7-hydroxyflavone (4), chrysin (5) and quercetin (6) (50 mg/kg). Compounds 1, 5 and 6 were found most active in both experiments in comparison with control group (p < 0.05). Figure optionsDownload full-size imageDownload as PowerPoint slide