Limits...
Protective Pleiotropic Effect of Flavonoids on NAD⁺ Levels in Endothelial Cells Exposed to High Glucose.

Boesten DM, von Ungern-Sternberg SN, den Hartog GJ, Bast A - Oxid Med Cell Longev (2015)

Bottom Line: Extending these studies, we here provide evidence that flavonoids are also able to protect endothelial cells against a high glucose induced decrease in NAD(+).In addition, we established that flavonoids are able to inhibit aldose reductase, the key enzyme in the polyol pathway.This mode of action enables flavonoids to ameliorate diabetic complications.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, Netherlands.

ABSTRACT
NAD(+) is important for oxidative metabolism by serving as an electron transporter. Hyperglycemia decreases NAD(+) levels by activation of the polyol pathway and by overactivation of poly(ADP-ribose)-polymerase (PARP). We examined the protective role of three structurally related flavonoids (rutin, quercetin, and flavone) during high glucose conditions in an in vitro model using human umbilical vein endothelial cells (HUVECs). Additionally we assessed the ability of these flavonoids to inhibit aldose reductase enzyme activity. We have previously shown that flavonoids can inhibit PARP activation. Extending these studies, we here provide evidence that flavonoids are also able to protect endothelial cells against a high glucose induced decrease in NAD(+). In addition, we established that flavonoids are able to inhibit aldose reductase, the key enzyme in the polyol pathway. We conclude that this protective effect of flavonoids on NAD(+) levels is a combination of the flavonoids ability to inhibit both PARP activation and aldose reductase enzyme activity. This study shows that flavonoids, by a combination of effects, maintain the redox state of the cell during hyperglycemia. This mode of action enables flavonoids to ameliorate diabetic complications.

No MeSH data available.


Related in: MedlinePlus

(a) Kinetics of porcine aldose reductase in the absence and presence of flavonoids. Data are expressed as mean ± standard deviation of at least three separate experiments. ∗P < 0.05 compared to control. (b) An example of a Michaelis Menten plot of aldose reductase in absence (filled circles) and presence of 5 μM quercetin (filled squares), 5 μM rutin (open triangles), 5 μM flavone (filled triangles), or 0.5 μM sorbinil (open circles). Data are expressed as mean ± standard error of at least three experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4477254&req=5

fig3: (a) Kinetics of porcine aldose reductase in the absence and presence of flavonoids. Data are expressed as mean ± standard deviation of at least three separate experiments. ∗P < 0.05 compared to control. (b) An example of a Michaelis Menten plot of aldose reductase in absence (filled circles) and presence of 5 μM quercetin (filled squares), 5 μM rutin (open triangles), 5 μM flavone (filled triangles), or 0.5 μM sorbinil (open circles). Data are expressed as mean ± standard error of at least three experiments.

Mentions: Quercetin, rutin, and flavone at a concentration of 5 μM decreased the Vmax of the aldose reductase catalysed conversion of DL-glyceraldehyde to glycerol. Sorbinil was used as a control and decreased both the Vmax and Km at a concentration of 0.5 μM. Rutin also showed a small but significant decrease of Km compared to the control (Figure 3).


Protective Pleiotropic Effect of Flavonoids on NAD⁺ Levels in Endothelial Cells Exposed to High Glucose.

Boesten DM, von Ungern-Sternberg SN, den Hartog GJ, Bast A - Oxid Med Cell Longev (2015)

(a) Kinetics of porcine aldose reductase in the absence and presence of flavonoids. Data are expressed as mean ± standard deviation of at least three separate experiments. ∗P < 0.05 compared to control. (b) An example of a Michaelis Menten plot of aldose reductase in absence (filled circles) and presence of 5 μM quercetin (filled squares), 5 μM rutin (open triangles), 5 μM flavone (filled triangles), or 0.5 μM sorbinil (open circles). Data are expressed as mean ± standard error of at least three experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4477254&req=5

fig3: (a) Kinetics of porcine aldose reductase in the absence and presence of flavonoids. Data are expressed as mean ± standard deviation of at least three separate experiments. ∗P < 0.05 compared to control. (b) An example of a Michaelis Menten plot of aldose reductase in absence (filled circles) and presence of 5 μM quercetin (filled squares), 5 μM rutin (open triangles), 5 μM flavone (filled triangles), or 0.5 μM sorbinil (open circles). Data are expressed as mean ± standard error of at least three experiments.
Mentions: Quercetin, rutin, and flavone at a concentration of 5 μM decreased the Vmax of the aldose reductase catalysed conversion of DL-glyceraldehyde to glycerol. Sorbinil was used as a control and decreased both the Vmax and Km at a concentration of 0.5 μM. Rutin also showed a small but significant decrease of Km compared to the control (Figure 3).

Bottom Line: Extending these studies, we here provide evidence that flavonoids are also able to protect endothelial cells against a high glucose induced decrease in NAD(+).In addition, we established that flavonoids are able to inhibit aldose reductase, the key enzyme in the polyol pathway.This mode of action enables flavonoids to ameliorate diabetic complications.

View Article: PubMed Central - PubMed

Affiliation: Department of Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, Netherlands.

ABSTRACT
NAD(+) is important for oxidative metabolism by serving as an electron transporter. Hyperglycemia decreases NAD(+) levels by activation of the polyol pathway and by overactivation of poly(ADP-ribose)-polymerase (PARP). We examined the protective role of three structurally related flavonoids (rutin, quercetin, and flavone) during high glucose conditions in an in vitro model using human umbilical vein endothelial cells (HUVECs). Additionally we assessed the ability of these flavonoids to inhibit aldose reductase enzyme activity. We have previously shown that flavonoids can inhibit PARP activation. Extending these studies, we here provide evidence that flavonoids are also able to protect endothelial cells against a high glucose induced decrease in NAD(+). In addition, we established that flavonoids are able to inhibit aldose reductase, the key enzyme in the polyol pathway. We conclude that this protective effect of flavonoids on NAD(+) levels is a combination of the flavonoids ability to inhibit both PARP activation and aldose reductase enzyme activity. This study shows that flavonoids, by a combination of effects, maintain the redox state of the cell during hyperglycemia. This mode of action enables flavonoids to ameliorate diabetic complications.

No MeSH data available.


Related in: MedlinePlus