In an earlier study, we showed that pterostilbene is an agonist for the peroxisome proliferator activated receptor alpha isoform (PPARa).  Activation of PPARa in rat hepatoma (H4IIEC3) cells by pterostilbene was compared with resveratrol and its methylether analogs, catechin, and epicathechin. The docking of these compounds into the PPARa ligand binding domain was also investigated.  Of the stilbenes, pterostilbene demonstrated the highest PPARa activation. Pterostilbene also showed decreases in PPARa activation paralleling those of Wy-1463, a synthetic PPARa ligand, in the presence of chenodeoxycholic acid, a specific inhibitor of PPARa. Real-time gene expression analysis revealed pterostilbene significantly and dose-dependently (at 10, 20 and 50 �M) increased PPARa gene expression, and exhibited greater induction than fenofibrate at 100 and 200 �M. Docking experiments revealed that the stilbenes docked in a similar manner in the benzophenone pocket, and had H-bond interaction with amino acids considered essential for PPARa activation. The catechins did not dock in the active pocket. In animal studies, up-regulation of hepatic PPARa mRNA expression was observed in hamsters fed diet supplemented with 2% of an ethanol extract of blueberry fruit pomace (BBX).  A significant negative correlation between liver LDL-cholesterol levels and PPARa expression was also observed.  Catechin, epicatechin, pterostilbene and resveratrol were quantitated in the BBX by GC-MS analysis.  Our studies provide further evidence that pterostilbene activates PPARa, and it may contribute to the hepatic LDL-cholesterol lowering and up-regulation of PPARa expression in hamsters fed BBX-supplemented diet.

Further studies demonstrate PPARa activation and gene expression up-regulation by pterostilbene

246th National Meeting (2013)

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