α-Glucosidase inhibitory effect of Potentilla astracanica and some isoflavones: Inhibition kinetics and mechanistic insights through in vitro and in silico studies

Int J Biol Macromol. 2017 Dec;105(Pt 1):1062-1070. doi: 10.1016/j.ijbiomac.2017.07.132. Epub 2017 Jul 27.

Abstract

α-Glucosidase enzyme inhibitors are clinically used for the treatment of Type 2 diabetes mellitus. We tested α-glucosidase inhibitory effects of Potentilla astracanica Jacq. extracts (1, 2), two compounds isolated from these extracts, prunetin 5-O-β-glucopyranoside (3) and genistein 5-O-β-glucopyranoside (4), and their aglycon forms (5 and 6). All the tested materials possessed remarkable α-glucosidase inhibitor activity compared to the positive control, acarbose. Genistein (6) showed the highest activity with an IC50 value of 1.47 (±0.11) μg/ml. An enzyme kinetics analysis revealed that 3 and 6 were uncompetitive, 5 was noncompetitive, and 4 was competitive inhibitors. Using molecular modeling techniques we tried to provide insight into molecular mechanisms of their activity and how allosteric binding of 6 affected binding interactions between the agonist (maltose) and the enzyme.

Keywords: Molecular dynamics; Potentilla; α-Glucosidase.

MeSH terms

  • Allosteric Regulation / drug effects
  • Catalytic Domain
  • Computer Simulation*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Isoflavones / pharmacology*
  • Kinetics
  • Models, Molecular
  • Plant Extracts / pharmacology*
  • Potentilla / chemistry*
  • alpha-Glucosidases / chemistry
  • alpha-Glucosidases / metabolism*

Substances

  • Glycoside Hydrolase Inhibitors
  • Isoflavones
  • Plant Extracts
  • alpha-Glucosidases