Research ArticleAging

Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence

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Science Translational Medicine  02 Oct 2013:
Vol. 5, Issue 205, pp. 205ra133
DOI: 10.1126/scitranslmed.3005870

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Cheers for Resveratrol Sulfates

Red wine drinkers rejoiced at the news that their chosen beverage contains the antioxidant resveratrol, a phytochemical that has health benefits and extends longevity in preclinical studies. But resveratrolߣs rapid metabolism appears to limit translation of its health benefits to humans, even if one chugs liters of red wine. Now, Patel et al. show that certain metabolites might contribute to resveratrol’s in vivo activity through metabolic regeneration of the parent compound.

The authors first detected and quantitated the sulfate and glucuronide conjugates of resveratrol in plasma and tissue after resveratrol ingestion, over time, by cancer patients and healthy control subjects. A daily dose of 1 g of resveratrol gave rise to plasma concentrations of these metabolites in the micromolar range. A pharmacokinetic analysis of resveratrol-3- and 4′-O-sulfate metabolites in mice revealed that sulfate hydrolysis generated free resveratrol, a reaction also observed in human colorectal cells in culture. The addition of resveratrol-sulfate metabolites to human cancer cells in culture correlated with an increase in autophagy and senescence, effects that were blocked with a sulfatase inhibitor that decreased the amounts of intracellular resveratrol. These findings suggest that resveratrol can enter tissues as a stable sulfate-conjugate. Selected cells then generate the free parent compound, which appears to be the form responsible for biological benefits.

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