Department of Microbiology, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea.
J Ethnopharmacol. 2011 Jan 27;133(2):788-95. doi: 10.1016/j.jep.2010.11.009. Epub 2010 Nov 9.
This study was conducted to elucidate the molecular mechanisms of SH21B, a traditional Korean herbal medicine commonly used for the treatment of obesity.
3T3-L1 preadipocytes were differentiated into adipocytes in the presence or absence of SH21B. Changes in mRNA or protein levels were analyzed using microarray, real-time polymerase chain reaction and western blotting analyses. Small interference (si)RNA transfection experiments were conducted to elucidate the essential role of β-catenin.
Microarray analyses showed that components of the WNT/β-catenin pathway including β-catenin, cyclin D1 and dishevelled 2 were up-regulated more than two-fold as a result of SH21B treatment during adipogenesis, which were confirmed by real-time PCR and western blotting. Modulation of the WNT/β-catenin pathway by SH21B resulted in the nuclear accumulation of β-catenin. Both intracellular lipid droplet formation and expressions of adipogenic genes including PPARγ, C/EBPα, FABP4 and LPL, which were inhibited by SH21B, were significantly recovered by β-catenin siRNA transfection.
SH21B modulates components of the WNT/β-catenin pathway during adipogenesis, and β-catenin plays a crucial role in the anti-adipogenic mechanism of SH21B.
本研究旨在阐明常用于治疗肥胖症的传统韩国草药 SH21B 的分子机制。
在存在或不存在 SH21B 的情况下，将 3T3-L1 前脂肪细胞分化为脂肪细胞。使用微阵列、实时聚合酶链反应和 Western blot 分析分析 mRNA 或蛋白质水平的变化。进行小干扰 (si)RNA 转染实验以阐明 β-连环蛋白的重要作用。
微阵列分析表明，WNT/β-连环蛋白通路的成分，包括β-连环蛋白、细胞周期蛋白 D1 和盘状结构域 2，在脂肪生成过程中由于 SH21B 处理而上调超过两倍，这通过实时 PCR 和 Western blot 得到证实。SH21B 对 WNT/β-连环蛋白通路的调节导致 β-连环蛋白的核积累。细胞内脂滴形成以及脂肪生成基因的表达，包括 PPARγ、C/EBPα、FABP4 和 LPL，这些基因受到 SH21B 的抑制，通过β-连环蛋白 siRNA 转染得到显著恢复。
SH21B 在脂肪生成过程中调节 WNT/β-连环蛋白通路的成分，β-连环蛋白在 SH21B 的抗脂肪生成机制中起关键作用。
