Polyphenolic flavonoids differ in their antiapoptotic efficacy in hydrogen peroxide-treated human vascular endothelial cells

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 similar to40% (P < 0.05) with distinct nuclear condensation and DNA fragmentation. In the H2O2 apoptosis model, the addition of 50 mumol/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 mumol/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.