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Biomed Pharmacother ; 94: 169-175, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28759754

RESUMEN

The chlorogenic acid (CGA) is a natural product isolated from Cecropia obtusifolia, which possesses several pharmacological properties, such as: anti-carcinogenic, neuroprotective, antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic. In relation to its effects on the hyperglycemia and hypertriglyceridemia, few is known about the mechanisms in which this compound may be acting, therefore, the aim of the present study was to determine if CGA acts as an insulin secretagogue increasing intracellular calcium concentrations ([Ca2+]i) in RINm5F cells; or as an insulin sensitizer and lipid-lowering agent stimulating the expression of PPARγ and PPARα, respectively, in 3T3-L1 adipocytes. As results, RINm5F cells treated with 200µM of CGA showed an increase in [Ca2+]i of 9-times versus control and 4-times as compared to positive control; in addition, an increase in insulin secretion was observed similarly to those of positive control. CGA also significantly increased the mRNA expression of PPARγ (150%) and GLUT4 (220%), as well PPARα (40%) and FATP (25%) as it was appreciated by RT-PCR. Additionally, a chemoinformatic analysis suggested that CGA has suitable physicochemical properties to be considered as leader bioactive molecule for the development of novel agents with similar properties. Together, our results indicate that CGA possesses multiple mechanisms of action for the development of highly effective therapeutics in the treatment of metabolic diseases such as type 2 diabetes.


Asunto(s)
Ácido Clorogénico/farmacología , Insulina/metabolismo , PPAR alfa/agonistas , PPAR gamma/agonistas , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Animales , Calcio/metabolismo , Ácido Clorogénico/química , Biología Computacional , Relación Dosis-Respuesta a Droga , Proteínas de Transporte de Ácidos Grasos/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Gliburida/farmacología , Humanos , Secreción de Insulina , Ratones , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Ratas
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