Quercetin enhances ABCA1 expression and cholesterol efflux through a p38-dependent pathway in macrophages

Chang, Yu-Cheng; Lee, Tzong‐Shyuan; Chiang, An-Na

doi:10.1194/jlr.m024471

Cited by 64 publications

(41 citation statements)

References 48 publications

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“…However, protein expression of SR‐BI was not affected by the presence of QA or quercetin. Previous studies have indicated that flavonoids may activate ABCA1 by up‐regulation of peroxisome proliferator‐activated receptor γ and liver X receptor α 21; another research study showed that quercetin enhances ABCA1 expression through a p38‐dependent pathway in macrophages 48. Our previous data indicated that both quercetin and exogenous N ‐acetylneuraminic acid could improve RCT‐related protein expression in apoE‐deficient mice 49.…”

Section: Discussionmentioning

confidence: 84%

Synthesis and cardiovascular protective effects of quercetin 7‐O‐sialic acid

Tian

Liu

Qin

et al. 2016

J Cellular Molecular Medi

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Oxidative stress and inflammation play important roles in the pathogenesis of cardiovascular disease (CVD). Oxidative stress‐induced desialylation is considered to be a primary step in atherogenic modification, and therefore, the attenuation of oxidative stress and/or inflammatory reactions may ameliorate CVD. In this study, quercetin 7‐O‐sialic acid (QA) was synthesized aiming to put together the cardiovascular protective effect of quercetin and the recently reported anti‐oxidant and anti‐atherosclerosis functions of N‐acetylneuraminic acid. The biological efficacy of QA was evaluated in vitro in various cellular models. The results demonstrated that 50 μM QA could effectively protect human umbilical vein endothelial cells (HUVEC, EA.hy926) against hydrogen peroxide‐ or oxidized low‐density lipoprotein‐induced oxidative damage by reducing the production of reactive oxygen species. QA attenuated hydrogen peroxide‐induced desialylation of HUVEC and lipoproteins. QA decreased lipopolysaccharide‐induced secretion of tumour necrosis factor‐α (TNF‐α) and monocyte chemoattractant protein‐1 (MCP‐1), and it significantly reduced the expression of intercellular adhesion molecule‐1, vascular cell adhesion molecule‐1, TNF‐α and MCP‐1. Furthermore, QA effectively promoted cholesterol efflux from Raw 264.7 macrophages to apolipoprotein A‐1 and high‐density lipoprotein by up‐regulating ATP‐binding cassette transporter A1 and G1, respectively. Results indicated that the novel compound QA exhibited a better capacity than quercetin for anti‐oxidation, anti‐inflammation, cholesterol efflux promotion and biomolecule protection against desialylation and therefore could be a candidate compound for the prevention or treatment of CVD.

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Section: Discussionmentioning

confidence: 84%

Synthesis and cardiovascular protective effects of quercetin 7‐O‐sialic acid

Tian

Liu

Qin

et al. 2016

J Cellular Molecular Medi

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“…The research from Ponnusamy et al points out that specific inhibition of the ERK pathway could block autophagy in the pathogenesis of renal fibroblasts 51. Furthermore, TAK1 is an important signalling pathway located upstream of p38 and ERK, which play critical roles in various types of physiological processes52, 53 . Kim SI showed that TGF‐β1 induced autophagy in mesangial cells via the TAK1‐MKK3‐p38 signalling pathway 54.…”

Section: Discussionmentioning

confidence: 99%

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Zhou

Fan

Zhong

et al. 2018

J Cellular Molecular Medi

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The ability of cisplatin (cis‐diamminedichloroplatinum II) toxicity to induce acute kidney injury (AKI) has attracted people's attention and concern for a long time, but its molecular mechanisms are still widely unknown. We found that the expression of transforming growth factor‐β (TGF‐β)‐activated kinase 1 (TAK1) could be increased in kidneys of mice administrated with cisplatin. Autophagy is an evolutionarily conserved catabolic pathway and is involved in various acute and chronic injuries. Moreover, p38 MAPK (mitogen‐activated protein kinase) and ERK regulate autophagy in response to various stimuli. Therefore, our hypothesis is that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells and thus exacerbating kidney damage. Here, BALB/c mice were intraperitoneally injected with a TAK1 inhibitor and were then administrated with sham or cisplatin at 20 mg/kg by intraperitoneal injection. Compared with mice in the vehicle cisplatin group, mice intraperitoneally injected with a TAK1 inhibitor were found to have lower serum creatinine and less tubular damage following cisplatin‐induced AKI. Furthermore, inhibition of TAK1 reduced p38 and Erk phosphorylation, decreased expression of LC3II and reversed the down‐regulation of P62 expression induced by cisplatin. The hypothesis was verified with tubular epithelial cells administrated with cisplatin in vitro. Finally, p38 inhibitor or ERK inhibitor abated autophagy activation and cell viability reduction in tubular epithelial cells treated with cisplatin plus TAK1 overexpression vector. Taken together, our results show that cisplatin activates TAK1, which phosphorylates p38 and ERK, leading to excessive autophagy of tubular epithelial cells that exacerbates kidney damage.

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“…Considering its lipid-lowering effects, quercetin may play an important role in the development of atherosclerosis by regulating RCT. An in vitro study has indicated that quercetin may activate ATP-binding cassette (ABC) A1 by up-regulating peroxisome proliferator-activated receptor γ (PPAR-γ) and liver X receptor α (LXR-α) [8], while other research showed that quercetin enhances ABCA1 expression through a p38-dependent pathway in macrophages [9]. Our previous data indicated that quercetin improves the expression of RCT-related proteins in apolipoprotein E-deficient ( apoE −/− ) mice [3].…”

Section: Introductionmentioning

confidence: 99%

Quercetin improves macrophage reverse cholesterol transport in apolipoprotein E-deficient mice fed a high-fat diet

Cui

Hou

et al. 2017

Lipids Health Dis

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BackgroundQuercetin, one of the most widely distributed flavonoids in plants, has been demonstrated to reduce hyperlipidaemia and atherosclerotic lesion formation. Reverse cholesterol transport (RCT) plays a crucial role in exporting cholesterol from peripheral cells, which is one mechanism utilized in the prevention and treatment of atherosclerosis. The aim of this study is to investigate whether quercetin reduces lipid accumulation by improving RCT in vivo.MethodsApolipoprotein E-deficient mice fed a high-fat diet were used to investigate the effect of quercetin on RCT by an isotope tracing method, and the underlying mechanisms were clarified by molecular techniques.ResultsThese novel results demonstrated that quercetin significantly improved [3H]-cholesterol transfer from [3H]-cholesterol-loaded macrophages to the plasma (approximately 34% increase), liver (30% increase), and bile (50% increase) and finally to the feces (approximately 40% increase) for excretion in apolipoprotein E-deficient mice fed a high-fat diet. Furthermore, quercetin markedly increased the cholesterol accepting ability of plasma and high-density lipoprotein (HDL) and dramatically decreased the content of malondialdehyde in plasma and oxidized phosphocholine carried by HDL. Therefore, the underlying mechanisms of quercetin in improving RCT may be partially due to the elevated cholesterol accepting ability of HDL, the increased expression levels of proteins related to RCT, such as ATP-binding cassettes (ABC) A1 and G1, and the improved antioxidant activity of HDL.ConclusionQuercetin accelerates RCT in an atherosclerosis model, which is helpful in clarifying the lipid-lowering effect of quercetin.

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Quercetin enhances ABCA1 expression and cholesterol efflux through a p38-dependent pathway in macrophages

Cited by 64 publications

References 48 publications

Synthesis and cardiovascular protective effects of quercetin 7‐O‐sialic acid

Synthesis and cardiovascular protective effects of quercetin 7‐O‐sialic acid

TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury

Quercetin improves macrophage reverse cholesterol transport in apolipoprotein E-deficient mice fed a high-fat diet

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