Inhibition of Hydrogen Peroxide-Induced Endothelial Apoptosis by 2′,4′,7-Trihydroxyflavanone, a Flavonoid Form

Abstract

Oxidative stress contributes to cellular injury following clinical and experimental ischemia/reperfusion episodes. Oxidative injury can induce cellular and subcellular damage that results in apoptotic cell death. We tested whether 2',4',7-trihydroxyflavanone, a synthetic flavonoid derivative, inhibits hydrogen peroxide (H(2)O(2))-induced toxicity in human umbilical endothelial cells (HUVECs). Cultured HUVECs were incubated for 30 minutes with 0.2 mM H(2)O(2) in the absence and presence of 2',4',7-trihydroxyflavanone at a non-toxic concentration of 50 microM. The effect of 2',4',7-trihydroxyflavanone on apoptosis parameters was compared with that of naringenin and two flavonol derivatives, 2',4',7-trihydroxyflavonol and 2',4',6-trihydroxyflavonol. H(2)O(2) induced cell death within 24 hours over the range of 0.05-1.0 mM, and decreased cell viability by approximately 30% at 0.2 mM. This cytotoxicity was associated with nuclear condensation and DNA fragmentation, indicating induction of apoptosis. 2',4',7-Trihydroxyflavanone, as well as naringenin, was effective as an inhibitor of oxidative stress, protecting cell viability with >/=85% viable cells compared with the control, and no apparent nuclear condensation or DNA fragmentation. In contrast, the flavonol derivatives had no such effect. In addition, immunocytochemical data and Western blot analysis revealed that, unlike flavonol derivatives, the expression of Bcl-2 was markedly up-regulated, and that the expression of Bax and activation of caspase-3 were strongly inhibited by this flavanone derivative, thereby implicating antioxidant activity-related anti-apoptotic mechanisms of 2',4',7-trihydroxyflavanone. These results indicate that the synthetic flavonoid derivative 2',4',7-trihydroxyflavanone is an effective antioxidant, preventing endothelial apoptosis induced by H(2)O(2).

Entacapone is an Antioxidant More Potent than Vitamin C and Vitamin E for Scavenging of Hypochlorous Acid and Peroxynitrite, and the Inhibition of Oxidative Stress-Induced Cell Death

“…H 2 O 2 is also quickly converted to toxic HOCl species. It is well known that H 2 O 2 -mediated oxidative stress can cause cell death [ 31 , 32 ]. We tested whether ENT could inhibit H 2 O 2 -induced toxicity in HUVECs.…”

“…For example, high levels of ROS-mediated oxidative stress can damage the structure and functions of endothelial cells, and contribute to pathogenesis of hypertension, diabetes, inflammation and atherosclerosis [ 58 , 59 ]. The assays of H 2 O 2 -induced death of endothelial cells or neuronal cells are commonly used in vitro models for determining antioxidant effects on oxidative stress [ 31 , 32 , 60 , 61 ]. Using these assays, other have shown that H 2 O 2 is highly permeable to cell membrane [ 62 ] and can increase production of O 2 − by activating NADPH oxidase and eNOS uncoupling [ 63 , 64 ].…”

Tetrahydronaphthalene as a precursor of new series of chalcones, flavanones, and flavone

“…1 Their extensive spectrum of biological activities has attracted considerable interest in medicinal chemistry and in organic synthesis. Indeed, chalcones have been shown to exhibit anticancer, 1−3 antiinflammatory, 4 antioxidant, 5 antifungal, 6 and antibacterial 7 activities. Therefore, a number of synthetic methods have been reported for the synthesis of these valuable derivatives, among which aldol and ClaisenSchmidt condensations are currently the common and simple protocols toward chalcones.…”

Effects of 4′,7-dimethoxyflavanone on cell cycle arrest and apoptosis in human breast cancer MCF-7 cells

“…Moreover, the anticancer activity of these synthetic compounds has been observed in various cancer cell lines in vitro (Liu et al, 1992;Min et al, 1997;Choi et al, 2004;Ying et al, 2008). We previously reported the production of synthetic flavonoids (Lee and Jung, 2005;Lee et al, 2007;Lee, 2008) that exert various biological activities in vitro (Choi et al, 2010) and have since been examining the phytoceutical applications of synthetic flavanone derivatives.…”