Limits...
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.

Show MeSH

Related in: MedlinePlus

Influence of the NOS inhibitor l-NAA on the effect of resveratrol on eNOS enzyme activity. EA.hy926 cells were treated with the indicated concentrations of resveratrol for 24 h. Then an [14C]l-arginine/[14C]l-citrulline conversion assay was performed as described both in the presence and absence of the NOS inhibitor l-NAA. [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
getmorefigures.php?uid=PMC4401015&req=5

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

Mentions: To demonstrate that [14C]l-citrulline production upon resveratrol treatment derives from eNOS enzyme activity the experiment was repeated in the presence of the NOS-inhibitor l-NAA (NG-Amino-l-arginine hydrochloride) (Figure 3). l-NAA reduced the basal and completely blocked the resveratrol-enhanced arginine conversion thereby confirming the NOS-specificity of the resveratrol effect.


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 the NOS inhibitor l-NAA on the effect of resveratrol on eNOS enzyme activity. EA.hy926 cells were treated with the indicated concentrations of resveratrol for 24 h. Then an [14C]l-arginine/[14C]l-citrulline conversion assay was performed as described both in the presence and absence of the NOS inhibitor l-NAA. [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 3: Influence of the NOS inhibitor l-NAA on the effect of resveratrol on eNOS enzyme activity. EA.hy926 cells were treated with the indicated concentrations of resveratrol for 24 h. Then an [14C]l-arginine/[14C]l-citrulline conversion assay was performed as described both in the presence and absence of the NOS inhibitor l-NAA. [14C]l-citrulline production was normalized to the untreated control (***p < 0.001; mean ± SD, n = 3).
Mentions: To demonstrate that [14C]l-citrulline production upon resveratrol treatment derives from eNOS enzyme activity the experiment was repeated in the presence of the NOS-inhibitor l-NAA (NG-Amino-l-arginine hydrochloride) (Figure 3). l-NAA reduced the basal and completely blocked the resveratrol-enhanced arginine conversion thereby confirming the NOS-specificity of the resveratrol effect.

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