Endothelial cells ability to deconjugate resveratrol metabolites to free resveratrol: possible role in tissue factor modulation

Identifier:  PC:3441

Handle: https://hdl.handle.net/20.500.11797/PC3441

Authors:  Fernández-Castillejo, Sara; Macià, Alba; Motilva, Maria-José; Catalán, Úrsula; Solà, Rosa

Abstract:
Scope. The antithrombotic effect of resveratrol (RV) and its forms remains unknown. The objective is to evaluate the effect of RV, its glucoside form piceid, and its biological metabolites (RV-3-O-β-D-Glucuronide, RV-4’-O-D-Glucuronide, and RV-3-O-Sulfate) on Tissue Factor (TF) modulation. Moreover, the endothelial metabolism of RV is assessed. Methods and results. Human aortic endothelial cells were incubated with trans-piceid, trans-RV, or its biological metabolites and stimulated with TNF-α. TF activity, protein, and mRNA expression were determined in cell lysates. Moreover, RV conjugation (phase II metabolism) to its sulphated or glucuronidated metabolites and their deconjugation to their parent compound (free RV) were also assessed in cell lysates and culture media. RV decreased TF activity, protein, and mRNA expression whereas piceid and RV metabolites showed no effects. RV-3-O-Sulfate was the main metabolite generated in the endothelium, while RV metabolites were deconjugated to free RV. Trans-RV and its trans-metabolites isomerization was observed generating their cis-forms. Conclusions. RV boasts antithrombotic effects modulating TF. RV metabolites and piceid did not show this effect. However, endothelial cells capacity to deconjugate RV metabolites to free RV indicates that RV metabolites can act as an endothelial reservoir for RV regeneration contributing to the antithrombotic effects of RV.