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Molecules 2013, 18(9), 10484-10496; doi:10.3390/molecules180910484

Salicortin-Derivatives from Salix pseudo-lasiogyne Twigs Inhibit Adipogenesis in 3T3-L1 Cells via Modulation of C/EBPα and SREBP1c Dependent Pathway

1
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Daehak-Dong, Gwanak-Gu, Seoul 151-742, Korea
2
Department of Agronomy and Medicinal Plant Resources, College of Life Sciences and Natural Resources, Gyeongnam National University of Science and Technology, Jinju 660-758, Korea
3
College of Pharmacy, Ajou University, Suwon 443-749, Korea
*
Author to whom correspondence should be addressed.
Received: 22 July 2013 / Revised: 26 August 2013 / Accepted: 27 August 2013 / Published: 30 August 2013
(This article belongs to the Section Natural Products)
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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-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.
Keywords: Salix pseudo-lasiogyne; Salicaceae; 3T3-L1; adipogenesis; adipocyte differentiation; C/EBPα; SREBP1c; obesity Salix pseudo-lasiogyne; Salicaceae; 3T3-L1; adipogenesis; adipocyte differentiation; C/EBPα; SREBP1c; obesity
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Lee, M.; Lee, S.H.; Kang, J.; Yang, H.; Jeong, E.J.; Kim, H.P.; Kim, Y.C.; Sung, S.H. Salicortin-Derivatives from Salix pseudo-lasiogyne Twigs Inhibit Adipogenesis in 3T3-L1 Cells via Modulation of C/EBPα and SREBP1c Dependent Pathway. Molecules 2013, 18, 10484-10496.

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