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

Mina Lee,Sang Sung,Jimmy Kang,Sang Lee,Heejung Yang,Eun Jeong,Hong Kim,Young Kim

doi:10.3390/molecules180910484

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.

Highlights

Obesity is a condition resulting from the excessive storage of fat in the body
During a search for anti-adipogenic phytochemicals from medicinal plants, we found five salicortin-derivatives isolated from S. pseudo-lasiogyne that can significantly inhibit adipocyte differentiation in 3T3-L1 cells
During screening to determine the anti-adipogenic activity of natural products, we observed that a methanolic extract of S. pseudo-lasiogyne twigs exhibited inhibitory activity on adipocyte differentiation in 3T3-L1 preadipocytes (Figure 1)

Summary

Introduction

Obesity is a condition resulting from the excessive storage of fat in the body. The prevalence of obesity is dramatically increasing and, in many industrialized countries, has become a health risk because of the high correlation between obesity and metabolic disorders such as type 2 diabetes, cardiovascular disease, hyperlipidemia, and hypertension [1,2]. Current remedies provided by the diet industry have failed to result in long-term maintenance of weight loss in obese patients and adverse effects of some remedies have been reported [3,4]. Adipose tissue growth involves formation of new adipocytes from precursor cells leading to an increase in both the number and size of adipocytes [5,6]. Regulation both size and number of adipocytes may provide a novel therapeutic approach to the treatment of obesity [7]

Results

Discussion

Conclusion