Planta Med 2014; 80 - SL43
DOI: 10.1055/s-0034-1394531

Following dietary polyphenols' fate after oral administration: A map of distribution of pterostilbene and one of its prodrugs in major organs of rat

M Azzolini 1, M La Spina 1, A Mattarei 2, C Paradisi 2, M Zoratti 1, 3, L Biasutto 1, 3
  • 1Department of Biomedical Sciences, University of Padua, Padua, Italy
  • 2Department of Chemical Sciences, University of Padua, Padua, Italy
  • 3CNR Neuroscience Institute, Padua, Italy

Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, Pts) is a natural dietary compound and the major polyphenolic component of blueberries. Several recent papers report that Pts contrasts inflammation and cancer and improves cognitive performance and short-term memory impaired by old age or neurodegeneration. The biological effects of polyphenols in vivo are now attributed mainly to interactions with proteins. Recent literature suggests that those of Pts may be ascribed to effects on epigenetic regulation, possibly mediated by MTA-1 and sirtuins, and perhaps by phosphodiesterases. Pharmacokinetic studies performed so far with Pts have focused on plasma levels, while none have reported tissue distribution, which is obviously most relevant for biological action in vivo. This study aimed to investigate tissue distribution of Pts and its metabolite(s) after oral administration in rats. The pharmacokinetic behaviour of Pts was then compared to that of a Pts-prodrug, developed in our lab with the aim of increasing the overall levels of non-metabolized Pts. After a single oral administration of Pts to rats, in all organs both Pts and its main in vivo metabolite, Pts-sulfate, reached a maximum concentration about 2h (tmax) after administration. The pharmacokinetic profile was very different in blood compared to the other tissues. When Pts-prodrug was administered, the tmax for Pts and Pts-sulfate was generally shifted to about 8 hours after administration. The absolute concentration (nmoles/gram) of Pts was significantly higher in the latter case for all organs except the liver, with AUC values approximately doubling, for example, in the brain, and Pts-sulfate concentrations reduced in all the organs examined. The increased non-metabolized Pts concentration in most of the organs, and especially in the brain, after administration of the Pts-prodrug suggest that it can be tested in in vivo cancer models and/or to ameliorate symptoms in elder animals showing cognitive deficits.

Keywords: Pterostilbene, tissue distribution, prodrug, pharmacokinetic