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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

Effect of incubation with 30 mM glucose on the expression of aldose reductase (a) and PARP-1 (b) after several incubation times. Effect of addition of flavonoids (compared to high glucose incubation) after 24 hours incubation is shown in (c) (aldose reductase) and (d) (PARP-1). Data are expressed as mean ± standard error from three independent experiments. ∗P < 0.05 compared to normal glucose incubation; ∗∗P < 0.05 compared to incubation with high glucose alone.
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fig1: Effect of incubation with 30 mM glucose on the expression of aldose reductase (a) and PARP-1 (b) after several incubation times. Effect of addition of flavonoids (compared to high glucose incubation) after 24 hours incubation is shown in (c) (aldose reductase) and (d) (PARP-1). Data are expressed as mean ± standard error from three independent experiments. ∗P < 0.05 compared to normal glucose incubation; ∗∗P < 0.05 compared to incubation with high glucose alone.

Mentions: In Figure 1, the effect of incubating HUVECs with 30 mM of glucose on gene expression of aldose reductase and PARP-1 is presented. It is visible that both aldose reductase and PARP-1 have a significant higher expression after 24-hour incubation compared to normal glucose. When flavonoids are coincubated during these 24 hours, there is no effect on aldose reductase expression compared to only high glucose incubation. Only quercetin seems to lower PARP-1 expression compared to high glucose incubation.


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)

Effect of incubation with 30 mM glucose on the expression of aldose reductase (a) and PARP-1 (b) after several incubation times. Effect of addition of flavonoids (compared to high glucose incubation) after 24 hours incubation is shown in (c) (aldose reductase) and (d) (PARP-1). Data are expressed as mean ± standard error from three independent experiments. ∗P < 0.05 compared to normal glucose incubation; ∗∗P < 0.05 compared to incubation with high glucose alone.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Effect of incubation with 30 mM glucose on the expression of aldose reductase (a) and PARP-1 (b) after several incubation times. Effect of addition of flavonoids (compared to high glucose incubation) after 24 hours incubation is shown in (c) (aldose reductase) and (d) (PARP-1). Data are expressed as mean ± standard error from three independent experiments. ∗P < 0.05 compared to normal glucose incubation; ∗∗P < 0.05 compared to incubation with high glucose alone.
Mentions: In Figure 1, the effect of incubating HUVECs with 30 mM of glucose on gene expression of aldose reductase and PARP-1 is presented. It is visible that both aldose reductase and PARP-1 have a significant higher expression after 24-hour incubation compared to normal glucose. When flavonoids are coincubated during these 24 hours, there is no effect on aldose reductase expression compared to only high glucose incubation. Only quercetin seems to lower PARP-1 expression compared to high glucose incubation.

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