Pterostilbene as a new natural product agonist for the peroxisome proliferator-activated receptor alpha (PPARα) isoform


Agnes M. Rimando, USDA, ARS, Natural Products Utilization Research Unit, P.O. Box 8048, University, MS 38677, Rangaswamy Nagmani, Product Development, Enzymatic Therapy, Inc, 825 Challenger Drive, Green Bay, WI 54311, and Dennis R. Feller, School of Pharmacy, University of Mississippi, Department of Pharmacology, University, MS 38677.
Resveratrol, a stilbenoid antioxidant found in grapes, wine and other berries, has been reported to have hypolipidemic properties. We investigated whether resveratrol and its three analogs would activate the peroxisome proliferator-activated receptor alpha (PPARα) isoform. This receptor is proposed to mediate the activity of lipid-lowering drugs such as the fibrates. Resveratrol and its three analogs; pterostilbene, piceatannol and resveratrol trimethyl ether were evaluated along with ciprofibrate (as a positive control) for the activation of endogenous PPARα in H4IIEC3 cells. Cells were transfected with a PPRE-AB (rat fatty acyl CoA β-oxidase response element) luciferase gene reporter construct. The analogs were tested at 1, 10, 100 and 300 μM concentrations. Of the four stilbenes, pterostilbene demonstrated the highest induction of PPARα showing 5- and 9-fold increases in luciferase activity at 100 and 300 μM, respectively, relative to control and vehicle (DMSO) alone. The maximal luciferase activity responses to pterostilbene are similar to those obtained with the hypolipidemic drug, ciprofibrate. These results suggest that pterostilbene acts as a PPARα agonist, like that of the fibrate class, and may be a more effective hypolipidemic agent than resveratrol.

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Division of Agricultural & Food Chemistry

The 228th ACS National Meeting, in Philadelphia, PA, August 22-26, 2004