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

Abstract

Curcumin was investigated as an inhibitor of glycogen synthase kinase-3β (GSK-3β) 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-3β followed by experimental in vitro and in vivo validations. Curcumin was found to optimally fit within the binding pocket of GSK-3β via several attractive interactions with key amino acids. Experimentally, curcumin was found to potently inhibit GSK-3β (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-3β.

Keywords::

• Curcumin
• glycogen synthase kinase
• docking simulation
• diabetes
• inflammation

Acknowledgements

This project was sponsored by the Deanship of Scientific Research at the University of Jordan (Grant No. 1102). The authors wish to thank the Deanship of Scientific Research and Hamdi-Mango Center for Scientific Research at the University of Jordan for their generous funds. The authors would like to thank also the OpenEye Scientific Software Corporation for providing free license of FRED software (FRED, version 2.1.2).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.