Naproxen and Cromolyn as New Glycogen Synthase Kinase 3 Inhibitors for Amelioration of Diabetes and Obesity: An Investigation by Docking Simulation and Subsequent In Vitro/In Vivo Biochemical Evaluation

作者：Motawi Tarek M K; Bustanji Yasser; EL Maraghy Shohda A^*; Taha Mutasem O; Al Ghussein Mohamed A S

来源：Journal of Biochemical and Molecular Toxicology, 2013, 27(9): 425-436.

DOI：10.1002/jbt.21503

• Naproxen
• Cromolyn
• Glycogen Synthase Kinase-3
• Docking Simulation
• Glycogen
• Resistin

Naproxen and cromolyn were investigated as new inhibitors of glycogen synthase kinase-3 (GSK-3) 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-3 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 mu M 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-3 inhibitors and can help in management of diabetes and obesity.

• 出版日期2013-9