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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 endothelial NO release. EA.hy926 cells were treated with the indicated concentrations of compounds for 24 h. Endothelial NO release was measured by incubation with the NO-sensitive fluorescent probe diaminofluorescein-FM. Fluorescence values were normalized to the number of viable cells as determined by resazurin staining (**p < 0.01; mean ± SD, n = 3).
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Figure 4: Influence of resveratrol and its metabolites on endothelial NO release. EA.hy926 cells were treated with the indicated concentrations of compounds for 24 h. Endothelial NO release was measured by incubation with the NO-sensitive fluorescent probe diaminofluorescein-FM. Fluorescence values were normalized to the number of viable cells as determined by resazurin staining (**p < 0.01; mean ± SD, n = 3).

Mentions: It is possible that the tested resveratrol metabolites are not directly changing eNOS enzyme activity but enhance the bioavailability of endothelial NO for example through the inhibition of superoxide-mediated NO inactivation [5]. Therefore, we determined the levels of endothelial NO release in EA.hy926 cells after treatment with resveratrol or resveratrol sulfate or glucuronide conjugates for 24 h (Figure 4). Resveratrol concentration-dependently increased endothelial NO release reaching significance and displaying a 5-fold increase at 30 μM. However, none of the tested resveratrol sulfate or glucuronide metabolites was able to elicit a significant change in endothelial NO release.


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 endothelial NO release. EA.hy926 cells were treated with the indicated concentrations of compounds for 24 h. Endothelial NO release was measured by incubation with the NO-sensitive fluorescent probe diaminofluorescein-FM. Fluorescence values were normalized to the number of viable cells as determined by resazurin staining (**p < 0.01; mean ± SD, n = 3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Influence of resveratrol and its metabolites on endothelial NO release. EA.hy926 cells were treated with the indicated concentrations of compounds for 24 h. Endothelial NO release was measured by incubation with the NO-sensitive fluorescent probe diaminofluorescein-FM. Fluorescence values were normalized to the number of viable cells as determined by resazurin staining (**p < 0.01; mean ± SD, n = 3).
Mentions: It is possible that the tested resveratrol metabolites are not directly changing eNOS enzyme activity but enhance the bioavailability of endothelial NO for example through the inhibition of superoxide-mediated NO inactivation [5]. Therefore, we determined the levels of endothelial NO release in EA.hy926 cells after treatment with resveratrol or resveratrol sulfate or glucuronide conjugates for 24 h (Figure 4). Resveratrol concentration-dependently increased endothelial NO release reaching significance and displaying a 5-fold increase at 30 μM. However, none of the tested resveratrol sulfate or glucuronide metabolites was able to elicit a significant change in endothelial NO release.

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