PPARγ ligand-binding activity of fragrin a isolated from mace (the aril of Myristica fragrans Houtt.)

Peroxisome proliferator-activated receptor-gamma (PPARy), 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 PPARγ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-l- (4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has PPARy ligand-binding activity, it was performed that GAL-4/PPARγ transactivation assay. PPARy ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and 10 μM, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of PPARy 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 PPARy agonist for the improvement of insulin resistance associated with type 2 diabetes.