title: Salicortin-derivatives from Salix pseudo-lasiogyne twigs inhibit adipogenesis in 3T3-L1 cells via modulation of C/EBPα and SREBP1c dependent pathway.
abstract: Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2',6'-O-acetylsalicortin (1), 2'-O-acetylsalicortin (2), 3'-O-acetylsalicortin (3), 6'-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2',6'-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC₅₀ value of 11.6 μM, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2',6'-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBPβ during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2',6'-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBPα and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Daehak-Dong, Gwanak-Gu, Seoul 151-742, Korea.
authors.forename: Mina
authors.initials: M
authors.lastname: Lee
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Jimmy
authors.initials: J
authors.lastname: Kang
authors.forename: Heejung
authors.initials: H
authors.lastname: Yang
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Jeong
authors.forename: Hong Pyo
authors.initials: HP
authors.lastname: Kim
authors.forename: Young Choong
authors.initials: YC
authors.lastname: Kim
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression / Q000187:drug effects; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D000432:Methanol / Q000737:chemistry; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry*; D032108:Salix / Q000737:chemistry*; D052616:Solid Phase Extraction; D012997:Solvents / Q000737:chemistry; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D005960:Glucosides; D010936:Plant Extracts; D012997:Solvents; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D000432:Methanol; C113068:salicortin