title: Dehydrodiconiferyl alcohol isolated from Cucurbita moschata shows anti-adipogenic and anti-lipogenic effects in 3T3-L1 cells and primary mouse embryonic fibroblasts.
abstract: A water-soluble extract from the stems of Cucurbita moschata, code named PG105, was previously found to contain strong anti-obesity activities in a high fat diet-induced obesity mouse model. One of its biological characteristics is that it inhibits 3T3-L1 adipocyte differentiation. To isolate the biologically active compound(s), conventional solvent fractionation was performed, and the various fractions were tested for anti-adipogenic activity using Oil Red O staining method. A single spot on thin layer chromatography of the chloroform fraction showed a potent anti-adipogenic activity. When purified, the structure of its major component was resolved as dehydrodiconiferyl alcohol (DHCA), a lignan, by NMR and mass spectrometry analysis. In 3T3-L1 cells, synthesized DHCA significantly reduced the expression of several adipocyte marker genes, including peroxisome proliferator-activated receptor γ (Pparg), CCAAT/enhancer-binding protein α (Cebpa), fatty acid-binding protein 4 (Fabp4), sterol response element-binding protein-1c (Srebp1c), and stearoyl-coenzyme A desaturase-1 (Scd), and decreased lipid accumulation without affecting cell viability. DHCA also suppressed the mitotic clonal expansion of preadipocytes (an early event of adipogenesis), probably by suppressing the DNA binding activity of C/EBPβ, and lowered the production level of cyclinA and cyclin-dependent kinase 2 (Cdk2), coinciding with the decrease in DNA synthesis and cell division. In addition, DHCA directly inhibited the expression of SREBP-1c and SCD-1. Similar observations were made, using primary mouse embryonic fibroblasts. Taken together, our data indicate that DHCA may contain dual activities, affecting both adipogenesis and lipogenesis.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: Junghun
authors.initials: J
authors.lastname: Lee
authors.forename: Donghyun
authors.initials: D
authors.lastname: Kim
authors.forename: Jonghyun
authors.initials: J
authors.lastname: Choi
authors.forename: Hyounjeong
authors.initials: H
authors.lastname: Choi
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.forename: Jinhyun
authors.initials: J
authors.lastname: Jeong
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Park
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D028464:Cucurbita / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects*; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D010636:Phenols; D010936:Plant Extracts; C080686:dehydrodiconiferyl alcohol