ReferenceID 4427

Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE-/- Mice

J Cell Mol Med

Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti-inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in

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Reference Id
4427
Evidence Id
21017
Core Evidence Id
21017
Source Reference Id
2135
Herb2 Reference Id
HBREF002932
Subject Paper Key
HBIN014294_33241629
Pubmed Id
33241629
Doi
10.1111/jcmm.16106
Paper Title
Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE-/- Mice
Paper Abstract
Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti-inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulatory effects of acacetin in maintaining endothelial cell function and further investigated whether the flavonoid could attenuate atherosclerosis in apolipoprotein E deficiency (apoE-/- ) mice. Different concentrations of acacetin were tested on EA.hy926 cells, either induced or non-induced by human oxidized low-density lipoprotein (oxLDL), to clarify its influence on cell viability, cellular reactive oxidative stress (ROS) level, apoptotic ratios and other regulatory effects. In vivo, apoE-/- mice were fed either a Western diet or a chow diet. Acacetin pro-drug (15 mg/kg) was injected subcutaneously two times a day for 12 weeks. The effects of acacetin on the atherosclerotic process, plasma inflammatory factors and lipid metabolism were also investigated. Acacetin significantly increased EA.hy926 cell viability by reducing the ratios of apoptotic and necrotic cells at 3 mumol/L. Moreover, 3 mumol/L acacetin clearly decreased ROS levels and enhanced reductase protein expression through MsrA and Nrf2 pathway through phosphorylation of Nrf2 and degradation of Keap1. In vivo, acacetin treatment remarkably attenuated atherosclerosis by increasing reductase levels in circulation and aortic roots, decreasing plasma inflammatory factor levels as well as accelerating lipid metabolism in Western diet-fed apoE-/- mice. Our findings demonstrate the anti-oxidative and anti-atherosclerotic effects of acacetin, in turn suggesting its potential therapeutic value in atherosclerotic-related cardiovascular diseases (CVD).
Journal
J Cell Mol Med
Publish Year
2021
Experiment Subject
mouse; human; ea.hy926 cell; ea.hy926 cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Apolipoprotein E Deficiency; Atherosclerosis; Myocarditis; Atherosclerotic-related Cardiovascular Diseases; Endothelial Cell Dysfunction
Paper Title Cn
Paper Title En
Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE-/- Mice
Bilingual Status
semi_complete