Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation |
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Authors: | Yasser Bustanji Mutasem O Taha Ihab M Almasri Mohamed AS Al-Ghussein Mohammad K Mohammad Hatim S Alkhatib |
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Institution: | 1. Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordanbustanji@ju.edu.jo;3. Faculty of Pharmacy, University of Jordan, Amman, 11942, Jordan |
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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. |
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Keywords: | Curcumin glycogen synthase kinase docking simulation diabetes inflammation |
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