RESUMO
Recently, obesity is a complex multifactorial chronic disease increasing the risk for type 2 diabetes, coronary heart disease and hypertension, and has become a major worldwide health problem. In the course of screening natural products employing 3T3-L1 cells as an in vitro system, the methanol extract of Idesia polycarpa Maxim. Fruits (Flacourtiaceae) significantly inhibited adipocyte differentiation by measuring lipid contents using oil red O staining. One new compound, 6-(oxymethyl)-2-hydroxyphenyl-O-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranoside (8), was isolated along with nine known compounds (1-7 and 9-10) from CHCl3 and n-BuOH fractions of the methanol extract of I. polycarpa fruits. Among them, idescarpin (1) with 1-hydroxy-6-oxo-2-cyclohexenecarboxylate moiety showed the most potent inhibitory activity on adipocyte differentiation with IC50 values of 23.2 µM. Idescarpin (1) dramatically suppressed the induction of C/EBPα expression, whereas it significantly increased the induction of PPARγ expression, supported by quantitative real time PCR and Western blot analysis. The down-regulation in mRNA levels of SREBP1c, SCD-1, and FAS by idescarpin (1) during adipocyte differentiation revealed that the inhibition of adipocyte differentiation was mediated by the regulation of lipogenesis. Taken together, we suggest that idescarpin (1) shows a great potential against obesity and diabetes though the anti-adipogenic activity and the up-regulation of PPARγ.
Assuntos
Fármacos Antiobesidade/química , Ácidos Cicloexanocarboxílicos/química , Dissacarídeos/química , Glucosídeos/química , Salicaceae/química , Células 3T3-L1 , Adipócitos/citologia , Adipogenia/efeitos dos fármacos , Animais , Fármacos Antiobesidade/isolamento & purificação , Fármacos Antiobesidade/farmacologia , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Ácidos Cicloexanocarboxílicos/isolamento & purificação , Ácidos Cicloexanocarboxílicos/farmacologia , Dissacarídeos/isolamento & purificação , Dissacarídeos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Frutas/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Receptor fas/genética , Receptor fas/metabolismoRESUMO
The methanolic extract of the bark of Betula platyphylla was found to suppress antigen mediated degranulation of RBL-2H3 cells. Four arylbutanoids (1-4) and eight diarylhepatonoids (5-12) were isolated from the methanolic extract using bioassay-guided fractionation. Among them, compounds 4 and 12 were isolated and assigned for the first time. Compounds 1, 2, 3, 5, 10, and 12 showed remarkable inhibitory activity against the degranulation of RBL-2H3 by antigen stimulation in a dose dependent manner at the concentrations ranging from 10 microM to 100 microM.
