Pterostilbene, a New Agonist for the Peroxisome Proliferator-Activated Receptor α-Isoform, Lowers Plasma Lipoproteins and Cholesterol in Hypercholesterolemic Hamsters

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 analogues (pterostilbene, piceatannol, and resveratrol trimethyl ether) would activate the peroxisome proliferator-activated receptor alpha (PPARalpha) 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 microM along with ciprofibrate (positive control), for the activation of endogenous PPARalpha in H4IIEC3 cells. Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA beta-oxidase response element)-luciferase gene reporter construct. Pterostilbene demonstrated the highest induction of PPARalpha showing 8- and 14-fold increases in luciferase activity at 100 and 300 microM, 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 microM. Hypercholesterolemic hamsters fed with pterostilbene at 25 ppm of the diet showed 29% lower plasma low density lipoprotein (LDL) cholesterol, 7% higher plasma high density lipoprotein (HDL) cholesterol, and 14% lower plasma glucose as compared to the 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. Results from in vitro studies showed that pterostilbene acts as a PPARalpha agonist and may be a more effective PPARalpha agonist and hypolipidemic agent than resveratrol. In vivo studies demonstrate that pterostilbene possesses lipid and glucose lowering effects.

A Stress-Inducible Resveratrol O-Methyltransferase Involved in the Biosynthesis of Pterostilbene in Grapevine

“…The anticancer, hypolipidemic, and antidiabetic properties of pterostilbene have recently attracted much interest (Rimando et al, 2005). In particular, the high hypolipidemic activity of pterostilbene may provide alternative treatments of dyslipidemia in the future.…”

“…Indeed, pterostilbene was found to decrease significantly plasma Glc levels in hyperglycemic rats (Manickam et al, 1997). Pterostilbene has also been reported to have hypolipidemic properties comparable to clinically used fibrate lipid-lowering drugs (Rimando et al, 2005). The targets of fibrate drugs are members of the peroxisome proliferator-activated receptor (PPAR) group of transcription factors, which play a major role in regulating lipoprotein metabolism (Kersten, 2008).…”

“…Activation of PPARa in mice and humans reduces hepatic triglyceride production and promotes plasma triglyceride clearance, leading to a reduction in plasma triglyceride levels. Pterostilbene was found to be very effective as a lipid/lipoproteinlowering agent in hypercholesterolemic hamsters, probably due to the fact that, like fibrate drugs, pterostilbene was shown to act as a PPARa agonist (Rimando et al, 2005). In addition, pterostilbene exhibits antioxidant and anticancer properties similar to those of resveratrol (Jang et al, 1997).…”

Animal Models as Tools for Translational Research: Focus on Atherosclerosis, Metabolic Syndrome and Type-II Diabetes Mellitus

“…Actually, cholesterol itself may not always be necessary for this phenotype, since a purified diet with no cholesterol but high concentrations of SF can promote more aortic cholesterol accumulation compared to a diet with both cocoa butter and 0.15% cholesterol [66]. Cholesterol-fed hamsters have been used to screen therapeutic anti-atherosclerotic and hypolipidemic properties of (phyto)medicines (e.g., [67,68]). Hamsters have been proposed as an animal model to evaluate diet-induced atherosclerosis since the 1980s [69].…”

Pterostilbene suppresses human endometrial cancer cells in vitro by down-regulating miR-663b

“…PT belongs to the class of stilbenes, a type of small molecular weight (approximately 200-300 g/mol) compounds that are widely distributed in plant sources, aromatherapy products, and dietary supplements [9] . PT has been widely used for its antihyperlipidemic, antidiabetic, and antioxidant properties in the treatment of fatty liver, diabetes, cardia-cerebrovascular disease and so on [10][11][12][13][14] . Some reports have also shown that PT may have anticancer activity.…”