Chalcona como modelo de estudo no receptor ativado por proliferador peroxissomal (PPAR)

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Peroxisome proliferators-activated receptors (PPAR) are genes regulators of important physiological processes, such as glucose homeostasis and inflammatory processes. Therefore, the development of ligants which behave as agonist for PPAR, have special interest in the research of the treatment of illnesses such as diabetes mellitus, dislypidemia and arteriosclerosis. Presently, the usage of troglitazone a synthetic ligant for PPAR-γ from thiazolidinediones (TZD) family is well known in the pharmacological marketplace. This type of drugs causes a sensibility to insulin and the improvement in treatment of diabetes mellitus 2. Despite some therapeutic limitations and some non desirable side effects as well. The flavonoids, more specifically chalcones, are also subject of interest due to their many pharmacological proprieties. The present thesis aims at the research of some kind chalcones, from the Helianthus annuus species, so that to evaluate their performances as possible PPAR agonists. Transfection assay in U937 cell were performed using expression vectors PPARγ α and δ and the PPARE-tk-luc repórter, it has been observed that as CF1 (Chalcone) as CF3 (4 metoxichalcone) presented an increase in the activation of PPAR- γ, besides the synergetic effect related to receptor activator by troglitazone. The same experiment was done with others subtypes PPARα and PPARδ. However, the final result was not same. Equally, there was not an increase of the transcription when other receptors such as ERα, ERβ,TRβ and gal-RXR were used, which demonstrates that CF1 and CF3 actually are selective agonists of PPAR- γ . The agonist activity of CF1 has also been proven in vitro by means of GST pull down assays, where it was observed that CF1 induced coativactor SRC1 recruitment and transactivation of PPAR- γ, which works accordingly with the transfection assays. The results of this study demonstrate that chalcones are agonists for PPAR- γ. In short, we hope that the results of the present work shall give a contribution to further researches in the usage of agonist molecules in PPAR in the treatment of chronic diseases such as diabetes mellitus and dislypidemia.

ASSUNTO(S)

tzd ppar diabetes melittus chalcone thiazolidinediones chalconas ciencias da saude ppar diabetes

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