Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation |
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Authors: | Bustanji Yasser Taha Mutasem O Almasri Ihab M Al-Ghussein Mohamed A S Mohammad Mohammad K Alkhatib Hatim S |
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Institution: | Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordan. bustanji@ju.edu.jo |
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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. |
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