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Endothelial Cells Deconjugate Resveratrol Metabolites to Free Resveratrol: A Possible Role in Tissue Factor Modulation
Author(s) -
FernándezCastillejo Sara,
Macià Alba,
Motilva MariaJosé,
Catalán Úrsula,
Solà Rosa
Publication year - 2019
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201800715
Subject(s) - metabolite , resveratrol , chemistry , biochemistry , metabolism , tissue factor , sulfation , antithrombotic , glucuronide , endothelial stem cell , angiogenesis , biology , medicine , coagulation , in vitro , cancer research
Scope The antithrombotic effects of resveratrol (RV) and its derivatives remain unknown. The objective is to evaluate the modulatory effects 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). Moreover, the endothelial metabolism of RV is assessed. Methods and results Human aortic endothelial cells (HAECs) are incubated with trans‐ piceid, trans‐ RV, or their biological metabolites and stimulated with tumor necrosis factor‐α (TNF‐α). TF activity, protein levels, and mRNA expression are determined in cell lysates. Moreover, RV conjugation (phase‐II‐metabolism) to its sulfated or glucuronidated metabolites and their deconjugation to their parent compound (free RV) are also assessed in cell lysates and culture media. RV decreased TF activity, protein levels, and mRNA expression, whereas piceid and RV metabolites (RVmet) had no effects. RV‐3‐ O ‐sulfate was the main metabolite generated in the endothelium, while RVmet are deconjugated to free RV. Isomerization of trans ‐RV and its trans ‐metabolites to their cis ‐forms is observed. Conclusions RV exerts antithrombotic effects by modulating TF. RVmet and piceid does not exert this effect. However, the capacity of endothelial cells to deconjugate RVmet to free RV indicates that RVmet function as an endothelial reservoir for RV regeneration, thus, contributing to the antithrombotic effects of RV.