Salicortin-derivatives from Salix pseudo-lasiogyne twigs inhibit adipogenesis in 3T3-L1 cells via modulation of C/EBPα and SREBP1c dependent pathway

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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- cyclohexenecarboxylate 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′-Oacetylsalicortin (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. © 2013 by the authors.

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Lee, M., Lee, S. H., Kang, J., Yang, H., Jeong, E. J., Kim, H. P., … Sung, S. H. (2013). Salicortin-derivatives from Salix pseudo-lasiogyne twigs inhibit adipogenesis in 3T3-L1 cells via modulation of C/EBPα and SREBP1c dependent pathway. Molecules, 18(9), 10484–10496. https://doi.org/10.3390/molecules180910484

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