title: 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 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.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Daehak-Dong, San 56-1, Sillim-Dong, Gwanak-Gu, Seoul 151-742, Republic of Korea.
authors.forename: Mina
authors.initials: M
authors.lastname: Lee
authors.forename: Hyang Hwa
authors.initials: HH
authors.lastname: Lee
authors.forename: Jin-Ku
authors.initials: JK
authors.lastname: Lee
authors.forename: Sang-Kyu
authors.initials: SK
authors.lastname: Ye
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004187:Disaccharides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008968:Molecular Conformation; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D031308:Salicaceae / Q000737:chemistry*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D003509:Cyclohexanecarboxylic Acids; D004187:Disaccharides; C491899:Fas protein, mouse; D005960:Glucosides; D047495:PPAR gamma; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D019014:fas Receptor; C584753:idescarpin; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase