Interplay between metabolism and transport of resveratrol

Resveratrol exhibits a variety of biological and pharmacological activities despite its extensive metabolism to sulfates and glucuronides in the intestine and liver. The metabolism of resveratrol is cell specific and strongly correlates with enzyme expression levels. However, a high rate of biotransformation, in concert with the action of the efflux transporters MRP2, MRP3, and ABCG2, reduces intracellular resveratrol concentrations, and may thereby decrease its pharmacological activity. Interestingly, biotransformation is also dependent on disease status. For example, significantly greater sulfation of resveratrol occurs in human breast tumor tissue than in adjacent nonmalignant tissue. The observed differences, however, do not correlate with the expression of sulfotransferases responsible for catalyzing resveratrol sulfation, but rather with significantly higher steroid sulfatase mRNA levels. The in vitro activity of resveratrol sulfates may not necessarily reflect their in vivo function, given the fact that ubiquitously existing human sulfatases can convert the metabolites back to active resveratrol in humans.