$PPAR_{\gamma}$ Ligand-binding Activity of Fragrin A Isolated from Mace (the Aril of Myristica fragrans Houtt.)

  • Lee, Jae-Young (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Kim, Ba-Reum (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Oh, Hyun-In (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Shen, Lingai (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Kim, Naeung-Bae (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Hwang, Jae-Kwan (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University)
  • Published : 2008.12.31

Abstract

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.

Keywords

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