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Naproxen and Cromolyn as New Glycogen Synthase Kinase 3β Inhibitors for Amelioration of Diabetes and Obesity: An Investigation by Docking Simulation and Subsequent In Vitro/In Vivo Biochemical Evaluation
Author(s) -
Motawi Tarek M. K.,
Bustanji Yasser,
ELMaraghy Shohda A.,
Taha Mutasem O.,
Al Ghussein Mohamed A. S.
Publication year - 2013
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21503
Subject(s) - in vivo , naproxen , glycogen synthase , gsk 3 , pharmacology , chemistry , insulin , in vitro , diabetes mellitus , ic50 , medicine , endocrinology , biochemistry , kinase , biology , alternative medicine , microbiology and biotechnology , pathology
Naproxen and cromolyn were investigated as new inhibitors of glycogen synthase kinase‐3β (GSK‐3β) in an attempt to explain their hypoglycemic properties. Study included simulated docking experiments, in vitro enzyme inhibition assay, and in vivo validations. Both drugs not only were optimally fitted within a GSK‐3β binding pocket via several attractive interactions with key amino acids but also exhibited potent in vitro enzymatic inhibitory activities of IC50 1.5 and 2.0 µM for naproxen and cromolyn, respectively. In vivo experiments illustrated that both drugs significantly reduced serum glucose and increased hepatic glycogen‐ and serum insulin levels in normal and type II diabetic Balb/c mice models. In obese animal model, both drugs exhibited significant reduction in mice weights, serum glucose, and resistin levels along with significant elevation in serum insulin, C‐peptide, and adiponectin values. It can be concluded that naproxen and cromolyn are novel GSK‐3β inhibitors and can help in management of diabetes and obesity. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:425–436, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21503