Scutellarin from Scutellaria baicalensis Suppresses Adipogenesis by Upregulating PPAR伪 in 3T3-L1 Cells

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• 作者：Kaihui Lu ; Miaomiao Han ; Hui Lin Ting ; Zeyu Liu ; Dawei Zhang
• 刊名：Journal of Natural Products
• 出版年：2013
• 出版时间：April 26, 2013
• 年：2013
• 卷：76
• 期：4
• 页码：672-678
• 全文大小：435K
• 年卷期：v.76,no.4(April 26, 2013)
• ISSN：1520-6025

文摘

Adipocyte dysfunction is a major cause of obesity, which is associated strongly with many disorders including psychological and medical morbidities, metabolic abnormalities, and cardiovascular diseases as well as a series of cancers. This study investigated the antiadipogenic activity of scutellarin (1) in 3T3-L1 preadipocytes as well as the underlying molecular mechanisms. It was observed that 1 reduced adipocyte differentiation of 3T3-L1 cells potently, as evidenced by a decrease in cellular lipid accumulation. At the molecular level, mRNA expression of the master adipogenic transcription factors, PPAR纬 and C/EBP伪, was decreased markedly. However, mRNA levels of C/EBP尾, the upstream regulator of PPAR纬 and C/EBP伪, were not decreased by 1. Moreover, a dose-dependent upregulation of PPAR伪 was observed for 1. Computational modeling indicated that 1 can bind to PPAR伪, 纬, and 未 each in a distinct manner, while it can activate PPAR伪 only by forming a hydrogen bond with Y464, thus stabilizing the AF-2 helix and activating PPAR伪. Therefore, these results suggest that 1, a major component of Scutellaria baicalensis, attenuates fat cell differentiation by upregulating PPAR伪 as well as downregulating the expression of PPAR纬 and C/EBP伪, thus showing therapeutic potential for obesity-related diseases.