Abstract
Nobiletin, a natural polymethoxylated flavonoid compound, has been shown to exert a wide range of biological activities. However, there is limited evidence on the molecular mechanisms by which nobiletin modulates endothelial cell function. Our aim was to investigate the potential of nobiletin to enhance endothelial cell functionality under nonstimulated and inflammatory conditions. To this end, gene expression relevant to nitric oxide (NO) production, endothelin 1 (ET-1), and antioxidant status in human endothelial cells EA.hy926 was determined using real-time PCR. The fluorescence probe 4,5-diaminofluorescein (DAF-2) was used to measure NO production. The results demonstrated significant upregulation of eNOS and antioxidant genes as well as downregulation of ET-1 by nobiletin under nonstimulated and TNF-α-stimulated inflammatory conditions. These findings suggest a promising protective effect of nobiletin with relevance for cardiovascular health, likely through the NO/ET-1 dynamics and Nrf2 signaling pathway.
Highlights
Epidemiological studies have suggested that the intake of citrus fruits is inversely associated with the risk of ischemic stroke [1] and coronary heart disease [2]
Tangeretin, and resveratrol were purchased from Extrasynthese (Genay, France). e purity of all compounds was above 97%
Differential Effects of Citrus Flavonoids on endothelial nitric oxide synthase (eNOS) Expression. e concentrations used in the following experiments were not toxic to cells (Figure S1)
Summary
Epidemiological studies have suggested that the intake of citrus fruits is inversely associated with the risk of ischemic stroke [1] and coronary heart disease [2]. Citrus fruits, such as oranges, grapefruit, lemons, limes, mandarins, bergamots and pomelos, are abundant in flavonoids, including hesperidin, hesperetin, naringin, naringenin, diosmin, quercetin, rutin, nobiletin, and tangeretin [3]. The consumption of citrus flavonoids is inversely associated with the risk of cardiovascular mortality [8]. Orange juice did not acutely affect endothelial function in men at moderate risk of cardiovascular disease [13]. Orange juice did not acutely affect endothelial function in men at moderate risk of cardiovascular disease [13]. erefore, the mechanisms by which citrus flavonoids modulate endothelial function remain to be elucidated
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