RESUMO
In our previous study, piperlonguminine from the fruit of Piper chaba was reported to promote adipogenesis in 3T3-L1 cells like the peroxisome proliferator-activated receptor-γ (PPARγ) agonist, troglitazone. In the present study, the mode of action of piperlonguminine in cells was examined. Piperlonguminine increased mRNA levels of adiponectin, glucose transporter 4, and fatty acid-binding protein (aP2). It also increased mRNA levels of PPARγ2 but, unlike troglitazone, piperlonguminine did not activate PPARγ directly in a nuclear receptor cofactor assay. Analyses of plasma from mice treated with piperlonguminine, piperine, and retrofractamide A, and an extract of the fruit, showed that concentrations of piperlonguminine were higher than those of piperine and retrofractamide A, and that the "area-under-the-curve" of piperine increased following in vivo administration of the extract.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Amidas/farmacocinética , Benzodioxóis/farmacocinética , Dioxolanos/farmacocinética , Extratos Vegetais/farmacocinética , Células 3T3-L1 , Adipócitos/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Alcaloides/farmacologia , Amidas/sangue , Amidas/isolamento & purificação , Animais , Área Sob a Curva , Benzodioxóis/sangue , Benzodioxóis/isolamento & purificação , Benzodioxóis/farmacologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Desoxiglucose/metabolismo , Dioxolanos/sangue , Dioxolanos/isolamento & purificação , Relação Dose-Resposta a Droga , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , Frutas/metabolismo , Humanos , Masculino , Camundongos , PPAR gama/agonistas , PPAR gama/genética , PPAR gama/metabolismo , Fitoterapia , Piper/química , Piperidinas/farmacologia , Extratos Vegetais/sangue , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Alcamidas Poli-Insaturadas/farmacologia , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triglicerídeos/metabolismoRESUMO
To search for a new class of antidiabetic compounds, effects of 44 flavonoids on the adipogenesis of 3T3-L1 cells were examined. Among them, 3,4',7-trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin concentration-dependently enhanced the accumulation of triglyceride, a marker of adipogenesis. With regard to structural requirements of flavonoids for the activity, it was fond that: (1) most flavonoids having hydroxy groups lacked the effect; (2) flavonols with methoxy groups showed stronger effects particularly those with a methoxy group at the 3-position; and (3) a methoxy group of flavonols at the B ring was also important. 3,4',7-Trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin significantly increased the amount of adiponectin released into the medium and the uptake of 2-deoxyglucose into the cells. Furthermore, tetramethylkaempferol and pentamethylquercetin also increased mRNA levels of adiponectin, glucose transporter 4 (GLUT4), and fatty acid-binding protein (aP2). Both compounds also increased the mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ2 and CCAAT/enhancer-binding protein (C/EBP)α, ß, and/or δ, although, different from troglitazone, they did not activate PPARγ directly in a nuclear receptor cofactor assay.
