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Polyphenolic Flavonoids Differ in Their Antiapoptotic Efficacy in Hydrogen Peroxide–Treated Human Vascular Endothelial Cells

Division of Life Sciences and Silver Biotechnology Research Center, Hallym University, Chuncheon, Korea and ^* Food and Nutrition, Cheju University, Cheju, Korea

²To whom correspondence should be addressed. E-mail: yhkang{at}hallym.ac.kr.

Oxidative injury induces cellular and nuclear damage that leads to apoptotic cell death. Agents or antioxidants that can inhibit production of reactive oxygen species can prevent apoptosis. We tested the hypothesis that flavonoids can inhibit H₂O₂-induced apoptosis in human umbilical vein endothelial cells. A 30-min pulse treatment with 0.25 mmol/L H₂O₂ decreased endothelial cell viability within 24 h by 40% (P < 0.05) with distinct nuclear condensation and DNA fragmentation. In the H₂O₂ apoptosis model, the addition of 50 µmol/L of the flavanol (-)epigallocatechin gallate and the flavonol quercetin, which have in vitro radical scavenging activity, partially (P < 0.05) restored cell viability with a reduction in H₂O₂-induced apoptotic DNA damage. In contrast, the flavones, luteolin and apigenin, at the nontoxic dose of 50 µmol/L, intensified cell loss (P < 0.05) after exposure to H₂O₂ and did not protect cells from oxidant-induced apoptosis. The flavanones, hesperidin and naringin, did not have cytoprotective effects. The antioxidants, (-)epigallocatechin gallate and quercetin, inhibited endothelial apoptosis, enhanced the expression of bcl-2 protein and inhibited the expression of bax protein and the cleavage and activation of caspase-3. Therefore, flavanols and flavonols, in particular (-)epigallocatechin gallate and quercetin, qualify as potent antioxidants and are effective in preventing endothelial apoptosis caused by oxidants, suggesting that flavonoids have differential antiapoptotic efficacies. The antiapoptotic activity of flavonoids appears to be mediated at the mitochondrial bcl-2 and bax gene level.

KEY WORDS: • flavonoids • endothelial apoptosis • hydrogen peroxide • bcl-2 • caspase-3

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