Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 94, Issue -, Pages 169-175Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.07.086
Keywords
Chlorogenic acid; Multitarget pharmaceuticals; Insulin secretagogue; Insulin sensitizers; PPAR gamma; PPAR alpha
Funding
- CONACyT [290649]
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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 PPAR gamma and PPAR alpha, respectively, in 3T3-L1 adipocytes. As results, RINm5F cells treated with 200 mu M 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 PPAR gamma (150%) and GLUT4 (220%), as well PPAR alpha (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. (C) 2017 Elsevier Masson SAS. All rights reserved.
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