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NADPH oxidase-dependent superoxide (O 2 •− ) production and oxidative stress play important roles in endothelial dysfunction and atherosclerosis. Herein, we investigated the potential effects of dietary quercetin, a flavonoid derived in the diet from vegetables and fruit, on vascular endothelial function and atherosclerosis in the high-fat diet (HFD)-fed apolipoprotein E-deficient (ApoE −/− ) mice. Dietary quercetin treatment significantly suppressed endothelial dysfunction and aortic atherosclerosis in HFD-fed ApoE −/− mice (P < 0.05, all cases). Mechanistic studies demonstrated that dietary quercetin significantly attenuated p47phox expression and inhibited NADPH oxidase-derived oxidative stress in the aortas of HFD-fed ApoE −/− mice, while the expression and activity of antioxidant enzyme heme oxygenase-1 (HO-1) was enhanced after quercetin treatment (P < 0.05, all cases). In vitro, it was found that quercetin significantly attenuated NADPH oxidase-derived O 2•− formation (75 ± 5.6% for quercetin versus 100 ± 6.0% for the control group, P < 0.01) in endothelial cells through induction of HO-1. In addition, the favorable effects of quercetin on oxidant (i.e., H 2 O 2 )-induced endothelial dysfunction could be eliminated by tin protoporphyrin IX (an HO-1 inhibitor) or HO-1-specific siRNA. Our results demonstrated the critical roles of NADPH oxidase and HO-1 for the indirect antioxidant properties of quercetin in vascular diseases.

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As an abundant protein in milk and blood serum, bovine serum albumin (BSA) contains various sites to bind a lot of bioactive components, generating BSA− monoligand complex. Demonstration of the interaction between BSA and bioactive components (such as heme, flavonoids) is important to develop effective carrier for the protection of bioactive ligands and to reduce cytotoxicity of heme. Herein, the bindings of BSA to quercetin and/or heme were investigated by multispectroscopic and molecular docking methods. The fluorescence of protein was significantly quenched by both quercetin and heme in a static mode (i.e., generation of BSA−ligand complex). Although quercetin had lower affinity to protein than heme, the interactions of both compounds with protein did locate in site I (i.e., subdomain IIA). BSA−diligand complex was successfully generated after the coaddition of quercetin and heme. The cytotoxicity of free heme to endothelial cells was reduced in the BSA−diligand complex relative to that of heme or BSA− monoligand complex, while the stability of bioactive quercetin was promoted in the complex relative to free flavonoid. The complex provided a better inhibition on the cytotoxicity of heme than BSA−monoligand complex, in which the copresence of quercetin played a vital role.