Quercetin Inhibited Endothelial Dysfunction and Atherosclerosis in Apolipoprotein E-Deficient Mice: Critical Roles for NADPH Oxidase and Heme Oxygenase-1

Abstract

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.

Systematic Pharmacology and GEO Database Mining Revealed the Therapeutic Mechanism of Xuefu Zhuyu Decoration for Atherosclerosis Cardiovascular Disease

“…In this study, quercetin could inhibit LPS-induced attachment of monocytes to HUVECs by downregulating expressions of VCAM-1 and ICAM-1 in vitro as well as suppress the expression of pro-inflammatory cytokines, which demonstrated the ability of quercetin to ameliorate endothelial dysfunction. Coincident with our results, quercetin was reported to remarkably suppress endothelial dysfunction and significantly attenuate atherosclerotic lesion progression in high-fat diet (HFD)-fed ApoE −/− mice (23). Likewise, it was demonstrated that quercetin had an inhibitory action on the expression of proinflammatory cytokines in hypercholesterolemic diet (HCD)-fed rats (24).…”

Therapeutic Effects and Safe Uses of Plant-Derived Polyphenolic Compounds in Cardiovascular Diseases: A Review

“… 62 Furthermore, a recent study conducted by Mengjuan et al, 2020 exhibited that quercetin significantly suppressed endothelial dysfunctioning and atherosclerotic plaque by attenuating the expression of p47phox and NADPH related oxidative damage attributed vital contribution of flavonoids in vascular diseases. 63 However, a double-blind randomized clinical trial has demonstrated the profound effect of quercetin on systolic blood pressure, but non-significant activity was analyzed on diastolic blood pressure and inflammatory cytokines. Thus, in vitro biological effects of quercetin are not proven in human studies and need to be elucidated further on different doses to obtain the better outcomes.…”

Screening of potential tropical fruits in protecting endothelial dysfunction in vitro

“…Recent review articles by Patel et al ( 39 ) and Deng et al ( 40 ) emphasize the protective role of quercetin in endothelial dysfunction from oxidative stress and its potential use as an antiatherosclerotic agent and in CVD prevention. Quercetin prevents endothelial dysfunction by competitively inhibiting myeloperoxidase-dependent HOCl generation and NADPH oxidase-dependent O 2 · – production that play a crucial role in atherosclerosis ( 41 , 42 ). Thus, our results are in line with the current evidence of using natural phytochemicals as a complementary remedy and in CVD prevention.…”