Pterostilbene as a new agonist for the peroxisome proliferator-activated receptor alpha isoform

Abstract

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 (PPARα) 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 PPARα in H4IIEC3 cells. Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA β-oxidase response element)—luciferase gene reporter construct. Of the four analogs, pterostilbene demonstrated the highest induction of PPARα 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 PPARα agonist, like that of the fibrate class, and may be a more effective hypolipidemic agent than resveratrol.

1 . A pharmaceutical composition comprising a therapeutically effective amount of pterostilbene and a pharmaceutically acceptable carrier.  
   
   
       2 . The pharmaceutical composition of  claim 1  wherein the therapeutically effective amount of pterostilbene is an amount sufficient to lower lipid levels in an individual.  
   
   
       3 . A nutraceutical composition comprising an amount of pterostilbene sufficient to lower lipid levels in an individual and a nutraceutically acceptable carrier.  
   
   
       4 . The nutraceutical composition of  claim 3  wherein the composition comprises extracts of grapes or berries of  Vaccinium  and a nutraceutically acceptable carrier.  
   
   
       5 . A method of lowering lipid levels in an individual comprising administering to an individual a therapeutically effective amount of the composition of  claim 1 .  
   
   
       6 . A method of treating dyslipidemias in individuals at risk of cardiovascular disease by administering to an individual a therapeutically effective amount of the composition of  claim 1 .  
   
   
       7 . A method of lowering lipid levels in an individual comprising administering to an individual an effective amount of the composition of  claim 3  or  claim 4 .  
   
   
       8 . A kit for the treatment of dyslipidemias, wherein the kit comprises: 
 a composition comprising an effective amount of pterostilbene according to  claim 1;     and a container housing the composition.    
   
   
       9 . A kit for lowering lipid levels in an individual, wherein the kit comprises: 
 a composition according  claim 3  or  claim 4;  and a container housing the composition.