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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 intracellular reactive oxygen species levels. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Intracellular ROS was measured by incubation with the fluorescent probe 2′,7′-dichloro-fluorescein-diacetate (DCF). (**p < 0.01, ***p < 0.001; mean ± SD, n = 4).
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Figure 5: Influence of resveratrol and its metabolites on intracellular reactive oxygen species levels. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Intracellular ROS was measured by incubation with the fluorescent probe 2′,7′-dichloro-fluorescein-diacetate (DCF). (**p < 0.01, ***p < 0.001; mean ± SD, n = 4).

Mentions: To elucidate if the tested resveratrol metabolites affect the cellular ROS detoxification systems, we investigated their effect on intracellular ROS levels. We treated EA.hy926 cells with resveratrol or resveratrol sulfate or glucuronide derivatives for 24 h and determined their ROS load by DCF staining (Figure 5). However, apart from the parent compound resveratrol none of the tested resveratrol metabolites was able to significantly change intracellular ROS levels. The fact that resveratrol, starting at 30 μM, increased intracellular ROS levels is in agreement with an already published study [35].


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 intracellular reactive oxygen species levels. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Intracellular ROS was measured by incubation with the fluorescent probe 2′,7′-dichloro-fluorescein-diacetate (DCF). (**p < 0.01, ***p < 0.001; mean ± SD, n = 4).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: Influence of resveratrol and its metabolites on intracellular reactive oxygen species levels. EA.hy926 cells were treated with the indicated concentrations of resveratrol or its metabolites for 24 h. Intracellular ROS was measured by incubation with the fluorescent probe 2′,7′-dichloro-fluorescein-diacetate (DCF). (**p < 0.01, ***p < 0.001; mean ± SD, n = 4).
Mentions: To elucidate if the tested resveratrol metabolites affect the cellular ROS detoxification systems, we investigated their effect on intracellular ROS levels. We treated EA.hy926 cells with resveratrol or resveratrol sulfate or glucuronide derivatives for 24 h and determined their ROS load by DCF staining (Figure 5). However, apart from the parent compound resveratrol none of the tested resveratrol metabolites was able to significantly change intracellular ROS levels. The fact that resveratrol, starting at 30 μM, increased intracellular ROS levels is in agreement with an already published study [35].

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