Autor(es): Dutra, Luiz A. [UNESP] ; Lacerda, Mariella G. ; Destro Inácio, Maiara [UNESP] ; Martins, Johnny W.L. [UNESP] ; Lopes Silva, Ana C. [UNESP] ; Bento da Silva, Patricia [UNESP] ; Chorilli, Marlus [UNESP] ; Amato, Angélica A. ; Baviera, Amanda M. [UNESP] ; Passarelli, Marisa ; Guido, Rafael V.C. ; Dos Santos, Jean L. [UNESP]
Data: 2022
Identificador Persistente: http://hdl.handle.net/11449/231602
Origem: Oasisbr
Assunto(s): Adipogenesis; Glucose homeostasis; HDL-C; PON1; PPARs; Stilbene
Made available in DSpace on 2022-04-29T08:46:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-01
Peroxisome proliferator-activated receptors are promising therapeutic targets for metabolic diseases, including obesity, diabetes, and dyslipidemia. This study describes the design, synthesis and pharmacological evaluation of stilbene-based compounds as dual PPARα/γ partial agonists with potency in the nanomolar range. In vitro and in vivo assays revealed that the lead compound (E)-4-styrylphenoxy-propanamide (5b) removed 14C-cholesterol from the foam cells through apolipoprotein A-I and High-Density Lipoprotein-2. In the high-fat diet-induced obesity mouse model, the oral administration of compound 5b increased HDL levels, paraoxonase-1 activity, and insulin sensitivity, and decreased glucose levels. Moreover, the adipogenesis pathway and triglyceride accumulation slightly changed in the adipocyte cells upon treatment with compound 5b, without affecting the body weight and adipose tissue in obese mice. Compound 5b did not affect the plasma levels of hepatic and renal injury biomarkers. Thus, stilbene-based compound 5b is a promising prototype for developing novel candidates to treat dyslipidemia and diabetes.
School of Pharmaceutical Science São Paulo State University (UNESP) Rodovia Araraquara Jaú Km 01 – s/n
Laboratory of Molecular Pharmacology Faculty of Health Sciences University of Brasilia Campos Univ. Darcy Ribeiro s/n – Asa Norte
Laboratório de Lípides (LIM 10) Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455 – Cerqueira César
Programa de Pós-Graduação em Medicina da Universidade Nove de Julho – UNINOVE Rua Vergueiro 235/249 – Liberdade
São Carlos Institute of Physics University of Sao Paulo, Av. João Dagnone 1100 – São Carlos-SP
School of Pharmaceutical Science São Paulo State University (UNESP) Rodovia Araraquara Jaú Km 01 – s/n
