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Impact of trans-resveratrol-sulfates and -glucuronides on endothelial nitric oxide synthase activity, nitric oxide release and intracellular reactive oxygen species.

Ladurner A, Schachner D, Schueller K, Pignitter M, Heiss EH, Somoza V, Dirsch VM - Molecules (2014)

Bottom Line: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts.In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels.Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. angela.ladurner@univie.ac.at.

ABSTRACT
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings.

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Influence of resveratrol and its metabolites on eNOS enzyme activity. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Then an [14C]l-arginine/[14C]l-citrulline conversion assay was performed as described. [14C]l-citrulline production was normalized to the untreated control (***p < 0.001; mean ± SD, n = 3).
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Figure 2: Influence of resveratrol and its metabolites on eNOS enzyme activity. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Then an [14C]l-arginine/[14C]l-citrulline conversion assay was performed as described. [14C]l-citrulline production was normalized to the untreated control (***p < 0.001; mean ± SD, n = 3).

Mentions: In a first experiment the [14C]l-arginine/[14C]l-citrulline conversion assay was utilized to measure eNOS enzyme activity (Figure 2). Treatment of endothelial cells with resveratrol concentration-dependently increased eNOS enzyme activity up to 1.64 fold at 100 μM compared to control conditions, thereby confirming the previously reported eNOS stimulation by resveratrol [10]. As resveratrol is metabolized in vivo, we studied the effect of metabolites on eNOS activity. We used resveratrol-3-sulfate, resveratrol-4′-sulfate, resveratrol disulfates, resveratrol-3-glucuronide and resveratrol-4′-glucuronide in concentrations from 1 to 100 μM in the same assay. However, none of the tested resveratrol sulfate or glucuronide metabolites was able to elicit a significant change in eNOS enzyme activity.


Impact of trans-resveratrol-sulfates and -glucuronides on endothelial nitric oxide synthase activity, nitric oxide release and intracellular reactive oxygen species.

Ladurner A, Schachner D, Schueller K, Pignitter M, Heiss EH, Somoza V, Dirsch VM - Molecules (2014)

Influence of resveratrol and its metabolites on eNOS enzyme activity. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Then an [14C]l-arginine/[14C]l-citrulline conversion assay was performed as described. [14C]l-citrulline production was normalized to the untreated control (***p < 0.001; mean ± SD, n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4401015&req=5

Figure 2: Influence of resveratrol and its metabolites on eNOS enzyme activity. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Then an [14C]l-arginine/[14C]l-citrulline conversion assay was performed as described. [14C]l-citrulline production was normalized to the untreated control (***p < 0.001; mean ± SD, n = 3).
Mentions: In a first experiment the [14C]l-arginine/[14C]l-citrulline conversion assay was utilized to measure eNOS enzyme activity (Figure 2). Treatment of endothelial cells with resveratrol concentration-dependently increased eNOS enzyme activity up to 1.64 fold at 100 μM compared to control conditions, thereby confirming the previously reported eNOS stimulation by resveratrol [10]. As resveratrol is metabolized in vivo, we studied the effect of metabolites on eNOS activity. We used resveratrol-3-sulfate, resveratrol-4′-sulfate, resveratrol disulfates, resveratrol-3-glucuronide and resveratrol-4′-glucuronide in concentrations from 1 to 100 μM in the same assay. However, none of the tested resveratrol sulfate or glucuronide metabolites was able to elicit a significant change in eNOS enzyme activity.

Bottom Line: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts.In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels.Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria. angela.ladurner@univie.ac.at.

ABSTRACT
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings.

Show MeSH
Related in: MedlinePlus