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Scope: Atherosclerotic cardiovascular disease is the most prevalent cause of mortality and morbidity. Fucoxanthin (FX) possesses anti-hypertensive and anti-obesity properties. However, the molecular mechanisms underlying the inhibitory effects of FX on oxidized low-density lipoprotein (oxLDL)-induced oxidative injuries in human endothelial cells are still largely unknown. This study aims to test the hypothesis that FX protects against oxLDL-induced oxidative stress by upregulating AMP-activated protein kinase (AMPK) and to explore the roles of cAMP response element binding protein (CREB) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)., Methods and Results: Human umbilical vein endothelial cells are treated with oxLDL in the presence or absence of FX. FX significantly increases AMPK phosphorylation. In addition, FX diminishes oxLDL-mediated nicotinamide adenine dinucleotide phosphate oxidase activation by inhibiting protein kinase C and subsequently inducing reactive oxygen species generation and impairing the activity of the endogenous antioxidant enzyme superoxidase dismutase. Furthermore, FX restores oxLDL-mediated dephosphorylation of phosphoinositide-3-kinase/Akt and decreases CREB and PGC-1α expression to nearly normal levels. Moreover, FX ameliorates the oxLDL-mediated suppression of mitochondrial function and apoptosis., Conclusion: These findings provide new insights into the possible molecular mechanisms by which FX mitigates oxLDL-induced endothelial oxidative stress and mitochondrial dysfunction., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Endothelial dysfunction is an important mechanism in the development of atherosclerosis and is thought to be critical for predicting cardiovascular diseases. Previous reports suggested that chlorogenic acid (CGA) is a potent antioxidant and anti-inflammatory compound. The molecular mechanisms underlying the inhibitory effects of CGA on oxLDL-induced oxidative injuries in human endothelial cells are still largely unknown. This study is aimed to test the hypothesis that CGA protects against oxLDL-facilitated oxidative stress by upregulating SIRT1 and to explore the role of AMPK/PGC-1 pathway and mitochondrial biogenesis., Methods and Results: HUVECs were treated with oxLDL in the presence or absence of CGA pretreatment. Our data indicated that CGA pretreatment increased SIRT1 deacetylase activity levels. In addition, CGA reversed oxLDL-impaired SIRT1 and AMPK/PGC-1 activity and mitigated oxLDL-induced oxidative stress and dysfunction of mitochondrial biogenesis. However, silencing SIRT1, AMPK, and PGC-1 abated the ability of CGA to protect against oxidative stress. Results from the present study also suggested that CGA inhibits oxLDL-induced endothelial apoptosis through modulating SIRT1 and AMPK/PGC-1 function., Conclusion: These findings provide new insights into possible molecular mechanisms by which CGA mitigates oxLDL-induced endothelial oxidative stress and mitochondrial dysfunction by activating SIRT1 and modulating the AMPK/PGC-1 signaling pathway., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scope: Atherosclerosis is believed to be an independent predictor of cardiovascular diseases. A growing body of evidence suggests that quercetin is a potent antioxidant and anti-inflammatory compound. The molecular mechanisms underlying its protective effects against oxidative stress in human endothelial cells remain unclear. This study was designed to confirm the hypothesis that quercetin inhibits oxidized LDL (oxLDL) induced endothelial oxidative damage by activating sirtuin 1 (SIRT1) and to explore the role of adenosine monophosphate activated protein kinase (AMPK), which is a negative regulator of Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) and free radicals., Methods and Results: Human umbilical vein endothelial cells were treated with oxLDL with or without quercetin pretreatment. We found that quercetin pretreatment increased SIRT1 mRNA expression. In fact, quercetin protected against oxLDL-impaired SIRT1 and AMPK activities and reduced oxLDL-activated NOX2 and NOX4. However, silencing SIRT1 and AMPK diminished the protective function of quercetin against oxidative injuries. The results also indicated that oxLDL suppressed AKT/endothelial NO synthase, impaired mitochondrial dysfunction, and enhanced reactive oxygen species formation, activating the Nuclear Factor Kappa B (NF-κB) pathway., Conclusion: These results provide new insight regarding the possible molecular mechanisms of quercetin. Quercetin suppresses oxLDL-induced endothelial oxidative injuries by activating SIRT1 and modulating the AMPK/NADPH oxidase/AKT/endothelial NO synthase signaling pathway., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)