PTEROSTILBENE AS A NEW AGONIST FOR THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ALPHA ISOFORM

摘要

Resveratrol, a stilbenoid antioxidant found in grapes, wine, peanuts and other berries, has been reported to have hypolipidemic properties. We investigated whether resveratrol and its three analogs (pterostilbene, piceatannol and resveratrol trimethyl ether) would activate the peroxisome proliferator-activated receptor alpha (PPARa) isoform. This nuclear receptor is proposed to mediate the activity of lipid-lowering drugs such as the fibrates. The four stilbenes were evaluated along with ciprofibrate (positive control) at 1, 10,100, 300 µM concentrations, for the activation of endogenous PPARa in H4IIEC3 cells. Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA ß-oxidase response element) - luciferase gene reporter construct. Of the four analogs, pterostilbene demonstrated the highest induction of PPARa showing 7- and 9-14 fold increases in luciferase activity at 100 and 300 µM, respectively, relative to control. The maximal luciferase activity responses to pterostilbene at 100 µM are similar to those obtained with the hypolipidemic drug, ciprofibrate. These results suggest that pterostilbene acts as a PPARa agonist, like that of the fibrate class, and may be a more effective hypolipidemic agent than resveratrol.