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

Figures & data

Figure 1.  (A) Molecular structure of curcumin, (B) Molecular structure of co-crystallized structure AR-A014418 [39].

Figure 2.  (A) Comparison between the docked pose (green) of the ligand AR-A014418 as produced by docking simulation and the crystallographic structure of this ligand (red) within the binding pocket of GSK-3β. (B) Detailed view of the co-crystallized structure (AR-A014418) and the corresponding interacting amino-acids within the binding site of GSK-3β.

Figure 3.  (A) Detailed view of the docked curcumin structure and the corresponding interacting amino-acid moieties within the binding site of GSK-3β. (B) Curcumin structure docked into the water-accessible surface (probe diameter 1.4 Å) within the active site of GSK-3β [39].

Figure 4.  Effect of curcumin on the relative activity of GSK-3β. Data are expressed as means of duplicates ± standard error of the measurements.

Figure 5.  Liver glycogen reserves in fasting 12 week old male Balb/c mice three hours after i.p. administration of vehicle control, 15, 30 and 60 mg/kg of curcumin normalized to mice weights (20 gm). Each result represents the average glycogen level from 5 mice. Error bars indicate the standard deviations of the measurements.

R Bhat, Y Xue, S Berg, S Hellberg, M Ormo, Y Nilsson, AC Radesater, E Jerning, PO Markgren, T Borgegard, M Nylof, A Gimenez-Cassina, F Hernandez, JJ Lucas, J Diaz-Nido, J Avila. Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem 2003;278:45937–45945.

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