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Title:   Author  item
                                            Rimando, Agnesitem
                                            RANGASWAMY, NAGMANI - ENZYMATIC THERAPY, INC.item
                                            FELLER, DENNIS - UNIVERSITY OF MISSISSIPPIitem
                                            Yokoyama, Wallace

                                                         - *Wally*
  Submitted to: Journal of Agricultural and Food Chemistry
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/15/2005
                                    Publication  Date: 5/1/2005
                                    Citation: Rimando, A.M., Rangaswamy, N., Feller, D.R., Yokoyama, W.H. 2005. Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamster. Journal of Agricultural and Food Chemistry.  53:3403-3407.Interpretive Summary: The nutraceutical compound resveratrol and three similar compounds were tested for their ability to activate a receptor involved in fatty acid and lipid metabolism.  The most active compound was pterostilbene, a compound commonly found in blueberries and certain other small fruits.  Pterostilbene was tested for its ability to lower cholesterol in hamsters.  It was more active than a cholesterol-lowering synthetic pharmaceutical, but appeared to have a similar mode of action in reducing chlolesterol.  It was particularly effective in lowering the low density lipoprotein cholesterol to high density lipoprotein cholesterol ratio. A low ratio correlates with reduced heart disease.
                                Technical 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 trimethylether) 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 at 1, 10, 100 and 300 uM along with ciprofibrate (positive control), for the activation of endogenous PPARa in H4IIEC3 cells.  Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA B-oxidase response element) - luciferase gene reporter construct.  Pterostilbene demonstrated the highest induction of PPARa showing 8- and 14-fold increases in luciferase activity at 100 and 300 uM, respectively, relative to the control.  The maximal luciferase activity responses to pterostilbene were higher than those obtained with the hypolipidemic drug, ciprofibrate (33910 and 19460 relative luciferase units, respectively), at 100 uM.  Hypercholesterolemic hamsters fed with pterostilbene at 25 ppm of the diet showed 29% lower plasma low density lipoprotein cholesterol, 7% higher plasma high density lipoprotein cholesterol, and 14% lower plasma glucose compared to control group.  The LDL/HDL ratio was also statistically significantly lower for pterostilbene, as compared to results for the control animals, at this diet concentration.  Taken collectively, these results suggest that pterostilbene acts as a PPARa agonist and possesses lipid and glucose lowering effects in vivo, like that of the fibrate class, and may be a more effective PPARa agonist and hypolipidemic agent than resveratrol.


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