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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

Flavonoids can protect cells under hyperglycemic stress in several ways. First, flavonoids are able to inhibit overactivation of PARP-1, preventing a decrease in NAD+ levels. Furthermore, flavonoids are able to inhibit aldose reductase activity, preventing an additional decrease in NAD+ and NADH levels. Also, because of their antioxidant properties, flavonoids are able to prevent damaging effects of oxidative stress. By a combination of all these effects flavonoids are able to protect cells against high glucose induced damage.
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fig4: Flavonoids can protect cells under hyperglycemic stress in several ways. First, flavonoids are able to inhibit overactivation of PARP-1, preventing a decrease in NAD+ levels. Furthermore, flavonoids are able to inhibit aldose reductase activity, preventing an additional decrease in NAD+ and NADH levels. Also, because of their antioxidant properties, flavonoids are able to prevent damaging effects of oxidative stress. By a combination of all these effects flavonoids are able to protect cells against high glucose induced damage.

Mentions: We conclude that flavonoids are able to exert pleiotropic protective effects under high glucose conditions (Figure 4). We observed that flavonoids were able to inhibit overactivation of PARP-1, thereby preventing a fall in NAD+ levels. Furthermore we observed that flavonoids are able to inhibit aldose reductase activity, preventing an additional decrease in NAD+ levels. Moreover, because of the known antioxidant properties of flavonoids they are also able to prevent the deleterious effects of reactive oxygen species which can be formed when a redox imbalance is present. In conclusion, the combination of all these effects is most likely the reason why flavonoids were able to protect endothelial cells against a high glucose induced drop in NAD+ levels in an in vitro system.


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)

Flavonoids can protect cells under hyperglycemic stress in several ways. First, flavonoids are able to inhibit overactivation of PARP-1, preventing a decrease in NAD+ levels. Furthermore, flavonoids are able to inhibit aldose reductase activity, preventing an additional decrease in NAD+ and NADH levels. Also, because of their antioxidant properties, flavonoids are able to prevent damaging effects of oxidative stress. By a combination of all these effects flavonoids are able to protect cells against high glucose induced damage.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Flavonoids can protect cells under hyperglycemic stress in several ways. First, flavonoids are able to inhibit overactivation of PARP-1, preventing a decrease in NAD+ levels. Furthermore, flavonoids are able to inhibit aldose reductase activity, preventing an additional decrease in NAD+ and NADH levels. Also, because of their antioxidant properties, flavonoids are able to prevent damaging effects of oxidative stress. By a combination of all these effects flavonoids are able to protect cells against high glucose induced damage.
Mentions: We conclude that flavonoids are able to exert pleiotropic protective effects under high glucose conditions (Figure 4). We observed that flavonoids were able to inhibit overactivation of PARP-1, thereby preventing a fall in NAD+ levels. Furthermore we observed that flavonoids are able to inhibit aldose reductase activity, preventing an additional decrease in NAD+ levels. Moreover, because of the known antioxidant properties of flavonoids they are also able to prevent the deleterious effects of reactive oxygen species which can be formed when a redox imbalance is present. In conclusion, the combination of all these effects is most likely the reason why flavonoids were able to protect endothelial cells against a high glucose induced drop in NAD+ levels in an in vitro system.

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