Naproxen and cromolyn as new glycogen synthase kinase 3ß inhibitors for amelioration of diabetes and obesity: an investigation by docking simulation and subsequent in vitro/in vivo biochemical evaluation.
J Biochem Mol Toxicol
; 27(9): 425-36, 2013 Sep.
Article
en En
| MEDLINE
| ID: mdl-23784744
ABSTRACT
Naproxen and cromolyn were investigated as new inhibitors of glycogen synthase kinase-3ß (GSK-3ß) 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-3ß 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-3ß inhibitors and can help in management of diabetes and obesity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Naproxeno
/
Cromolin Sódico
/
Glucógeno Sintasa Quinasa 3
/
Diabetes Mellitus
/
Obesidad
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biochem Mol Toxicol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
TOXICOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Egipto