Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation

J Enzyme Inhib Med Chem. 2009 Jun;24(3):771-8. doi: 10.1080/14756360802364377.

Abstract

Curcumin was investigated as an inhibitor of glycogen synthase kinase-3beta (GSK-3beta) in an attempt to explain some of its interesting multiple pharmacological effects, such as its anti-diabetic, anti-inflammatory, anti-cancer, anti-malarial and anti-alzheimer's properties. The investigation included simulated docking experiments to fit curcumin within the binding pocket of GSK-3beta followed by experimental in vitro and in vivo validations. Curcumin was found to optimally fit within the binding pocket of GSK-3beta via several attractive interactions with key amino acids. Experimentally, curcumin was found to potently inhibit GSK-3beta (IC50 = 66.3 nM). Furthermore, our in vivo experiments illustrated that curcumin significantly increases liver glycogen in fasting Balb/c mice. Our findings strongly suggest that the diverse pharmacological activities of curcumin are at least partially mediated by inhibition of GSK-3beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / pathology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Binding Sites
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Mice
  • Mice, Inbred BALB C
  • Molecular Dynamics Simulation*
  • NF-kappa B / metabolism
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • NF-kappa B
  • Protein Kinase Inhibitors
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3
  • Curcumin