Anti-adipogenic activity of compounds isolated from Idesia polycarpa on 3T3-L1 cells

Abstract 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 -β- d -glucopyranosyl-(1 → 6)-β- d -glucopyranoside ( 8 ), was isolated along with nine known compounds ( 1 – 7 and 9 – 10 ) from CHCl 3 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 IC 50 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.