Anthocyanins Induce Cholesterol Efflux from Mouse Peritoneal Macrophages

It is widely accepted that stimulation of reverse cholesterol transport, the efflux of excess cholesterol from peripheral tissues and transferring it to the liver for biliary excretion, is becoming an important component in reducing excess cholesterol deposition in atherosclerotic plaques. The ATP-binding cassette transporter has been identified as a key regulator of macrophage cholesterol efflux and apoAI-mediated reverse cholesterol transport. In vivo studies have documented anthocyanins, a large group of naturally phenolic compounds rich in plants, possess substantial capacities in improving plasma cholesterol levels. In this study, we investigated the potential role of anthocyanins in modulating cholesterol efflux from mouse peritoneal macrophages and macrophage-derived foam cells and the possible molecular mechanism linking ABCA1 to cholesterol efflux. Incubation of the mouse peritoneal macrophages and macrophage-derived foam cells with cyanidin-3-O-β-glucoside and peonidin-3-O-β-glucoside led to dose-dependent (1–100 μm) induction in cholesterol efflux and ABCA1 mRNA expression, and this effect could be blocked by the ABCA1 inhibitor 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, disodium salt, and a general inhibitor of gene transcription actinomycin D. Treatment of the macrophages with anthocyanins also activated peroxisome proliferator-activated receptor γ, liver X receptor α mRNA expression, and their mediated gene expression. Addition of geranylgeranyl pyrophosphate ammonium salt or GW9662 markedly inhibited the anthocyanin-induced increase of ABCA1 gene expression and apoAI-mediated cholesterol efflux. These data demonstrated that anthocyanin induces cholesterol efflux from mouse peritoneal macrophages and macrophage-derived foam cells and that stimulation of cholesterol efflux by anthocyanin is mediated, at least in part, by peroxisome proliferator-activated receptor γ-liver X receptor α-ABCA1 signaling pathway activation.

• Publication year

  2005

• Venue

  Journal of Biological Chemistry

• Publication date

  2005-11-04

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1074/jbc.M505047200PMID 16107338
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• IL-13受体α2降低血吸虫病肉芽肿的炎症反应并延长宿主存活时间[英]/Mentink-Kane MM,Cheever AW，Thompson RW，et al//Proc Natl Acad Sci U S A

  2005cited by this paper
• Anthocyanins and other flavonoids.

  2004cited by this paper
• LXR/RXR ligand activation enhances basolateral efflux of beta-sitosterol in CaCo-2 cells.

  2004cited by this paper
• Probucol Inhibits ABCA1-Mediated Cellular Lipid Efflux

  2004cited by this paper
• Cyclosporin A Traps ABCA1 at the Plasma Membrane and Inhibits ABCA1-Mediated Lipid Efflux to Apolipoprotein A-I

  2004cited by this paper
• Oxidative DNA damage in circulating mononuclear blood cells after ingestion of blackcurrant juice or anthocyanin-rich drink.

  2004cited by this paper
• Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3-L1 cells Published, JLR Papers in Press, May 16, 2003. DOI 10.1194/jlr.M200466-JLR200

  2003cited by this paper
• PPAR agonists protect mesangial cells from interleukin 1beta-induced intracellular lipid accumulation by activating the ABCA1 cholesterol efflux pathway.

  2003cited by this paper
• Supplementation of diets with the black rice pigment fraction attenuates atherosclerotic plaque formation in apolipoprotein e deficient mice.

  2003cited by this paper
• Cyanidin and cyanidin 3-O-β-D-glucoside as DNA cleavage protectors and antioxidants

  2003cited by this paper
• Peroxisome Proliferator-Activated Receptor &agr; Reduces Cholesterol Esterification in Macrophages

  2003cited by this paper
• Ceramide Enhances Cholesterol Efflux to Apolipoprotein A-I by Increasing the Cell Surface Presence of ATP-binding Cassette Transporter A1*

  2003cited by this paper
• Liver X receptor and retinoic X receptor mediated ABCA1 regulation and cholesterol efflux in macrophage cells-messenger RNA measured by branched DNA technology.

  2002cited by this paper
• Unsaturated Fatty Acids Inhibit Cholesterol Efflux from Macrophages by Increasing Degradation of ATP-binding Cassette Transporter A1*

  2002cited by this paper
• Transcription inhibitor actinomycin-D abolishes the cardioprotective effect of ischemic reconditioning.

  2002cited by this paper
• A PPARγ-LXR-ABCA1 Pathway in Macrophages Is Involved in Cholesterol Efflux and Atherogenesis

  2001cited by this paper
• Anthocyanins and other flavonoids.

  2001cited by this paper
• PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway

  2001cited by this paper
• A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.

  2001cited by this paper
• Sterol-dependent transactivation of the ABC1 promoter by the liver X receptor/retinoid X receptor.

  2000cited by this paper
• The role of plaque rupture and thrombosis in coronary artery disease.

  2000cited by this paper
• Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha.

  2000cited by this paper
• ABCA1 Is the cAMP-inducible Apolipoprotein Receptor That Mediates Cholesterol Secretion from Macrophages*

  2000cited by this paper
• PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway.

  2000cited by this paper
• ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins.

  2000cited by this paper
• Uptake of oxidized LDL by macrophages differs from that of acetyl LDL and leads to expansion of an acidic endolysosomal compartment.

  1999cited by this paper
• PPARγ Activation in Human Endothelial Cells Increases Plasminogen Activator Inhibitor Type-1 Expression PPARγ as a Potential Mediator in Vascular Disease

  1999cited by this paper
• The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway.

  1999cited by this paper
• PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease.

  1999cited by this paper
• Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency

  1999cited by this paper
• The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease

  1999cited by this paper
• Macrophages in Human Atheroma Contain PPARγ: Differentiation-Dependent Peroxisomal Proliferator-Activated Receptor γ (PPARγ) Expression and Reduction of MMP-9 Activity through PPARγ Activation in Mononuclear Phagocytes in Vitro

  1998cited by this paper
• Cholesterol metabolism and efflux in human THP-1 macrophages.

  1998cited by this paper
• Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro.

  1998cited by this paper
• Atherosclerosis is an Inflammatory Disease

  1998cited by this paper
• Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics.

  1995cited by this paper
• A macrophage receptor for oxidized low density lipoprotein distinct from the receptor for acetyl low density lipoprotein: partial purification and role in recognition of oxidatively damaged cells.

  1995cited by this paper
• Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP).

  1994cited by this paper
• The pathogenesis of atherosclerosis: a perspective for the 1990s

  1993cited by this paper
• Why do plaques rupture?

  1992cited by this paper
• Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity.

  1989cited by this paper
• Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability.

  1986cited by this paper
• A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.

  1976cited by this paper
• Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts.

  1976cited by this paper
• CIRCULATION

  1964cited by this paper
• Protein measurement with the Folin phenol reagent.

  1951cited by this paper
• Arteriosclerosis

  1925cited by this paper

• Phytochemicals Alter Foam Cell Formation and Macrophage Cholesterol Efflux

  2026cites this paper
• The phytohormone abscisic acid enhances remyelination in mouse models of multiple sclerosis

  2024cites this paper
• From Orchard to Wellness: Unveiling the Health Effects of Sweet Cherry Nutrients

  2024cites this paper
• Roles of CcDFR and CcOMT9 in the cyanidin biosynthesis and development of Cordyceps cicadae

  2024cites this paper
• Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches

  2024cites this paper
• The Effect of Anthocyanins Black Rice Bran Extract (ABRiBE) on Colorectal Cancer Cell Proliferation and ABCA1 Gene Expression in the HT-29 Cell Line

  2024influential citation
• Anthocyanins in Vascular Health and Disease: Mechanisms of Action and Therapeutic Potential

  2024cites this paper
• Regulation of Cholesterol Transporters by Nuclear Receptors

  2023cites this paper
• Efek ekstrak umbi ubi jalar ungu (Ipomoea batatas) terhadap peningkatan ekspresi ABCA1 pada tikus model dislipidemia

  2023cites this paper
• Cholesterol-Lowering Activity of Vitisin A Is Mediated by Inhibiting Cholesterol Biosynthesis and Enhancing LDL Uptake in HepG2 Cells

  2023cites this paper
• Purple Sweet Potato Powder Containing Anthocyanin Mitigates High-Fat-Diet-Induced Dry Eye Disease

  2023cites this paper
• Effects of anthocyanin supplementation on blood lipid levels: a systematic review and meta-analysis

  2023cites this paper
• Blueberry Consumption and Changes in Obesity and Diabetes Mellitus Outcomes: A Systematic Review

  2022cites this paper
• Ursolic acid enhances the effect of exercise training on vascular aging by reducing oxidative stress in aged type 2 diabetic rats

  2022cites this paper
• Cyanidin-3-O-β-glucoside protects against pulmonary artery hypertension induced by monocrotaline via the TGF-β1/p38 MAPK/CREB signaling pathway

  2021cites this paper
• Effects of phytochemicals on macrophage cholesterol efflux capacity: Impact on atherosclerosis

  2021influential citation
• protects against pulmonary artery hypertension induced by monocrotaline via the TGF‑ β 1/p38 MAPK/CREB signaling pathway

  2021cites this paper
• Bioactivity of Dietary Polyphenols: The Role in LDL-C Lowering

  2021cites this paper
• Seasonal Consumption of Cherries from Different Origins Affects Metabolic Markers and Gene Expression of Lipogenic Enzymes in Rat Liver: A Preliminary Study

  2021cites this paper
• Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu.

  2021cites this paper
• Phloretin suppresses neuroinflammation by autophagy-mediated Nrf2 activation in macrophages

  2021cites this paper
• Blueberry intervention improves metabolic syndrome risk factors: systematic review and meta-analysis.

  2021cites this paper
• Antioxidant Properties of Anthocyanins and Their Mechanism of Action in Atherosclerosis.

  2021cites this paper
• Cyanidin-3-O-β-glucoside polarizes LPS-induced M1 into M2 Macrophage in J774 cells via PPARγ-mediated NF-κB and STAT6 signaling pathway

  2021cites this paper
• Effects of strawberry intervention on cardiovascular risk factors: a meta-analysis of randomised controlled trials

  2020cites this paper
• The roles of the gut microbiota–miRNA interaction in the host pathophysiology

  2020cites this paper
• Insights into the potential benefits of black soybean (Glycine max L.) polyphenols in lifestyle diseases.

  2020cites this paper
• Anthocyanin supplementation at different doses improves cholesterol efflux capacity in subjects with dyslipidemia—a randomized controlled trial

  2020cites this paper
• A Review of Biologically Active Natural Products from Mediterranean Wild Edible Plants: Benefits in the Treatment of Obesity and Its Related Disorders

  2020cites this paper
• Cherry

  2020cites this paper
• Chronic Marijuana Use Moderates the Correlations of Serum Cholesterol with Systemic Mitochondrial Function and Fluid Cognition.

  2020influential citation
• Novel insights in health-promoting properties of sweet cherries

  2020cites this paper
• Allium sativum, Hylocereus polyrhizus and its Combination Effectiveness on Lipid Profiles and Number of Foam Cells in Rats with Dyslipidemia

  2019cites this paper
• Bilberries and blueberries as potential modulators of type 2 diabetes and associated diseases

  2019cites this paper
• Analysis of Low Molecular Weight Substances and Related Processes Influencing Cellular Cholesterol Efflux

  2019cites this paper
• Impact of natural products on the cholesterol transporter ABCA1.

  2019cites this paper
• Hypouricemic and nephroprotective roles of anthocyanins in hyperuricemic mice.

  2019cites this paper
• Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products

  2019cites this paper
• Effect of Purple Sweet Potato Extract (Ipomoea batatas L) on Zebrafish (Danio rerio) By Diet Induced Obesity

  2019cites this paper
• Natural polyphenols as sirtuin 6 modulators

  2018cites this paper
• Beneficial effects of cherry consumption as a dietary intervention for metabolic, hepatic and vascular complications in type 2 diabetic rats

  2018cites this paper
• Effets de deux modalités d'entraînement et d'une complémentation à base d'extraits végétaux sur le développement du diabète de type 2 : Physiologie

  2018cites this paper
• Corrigendum: Factors Affecting Quality and Health Promoting Compounds during Growth and Postharvest Life of Sweet Cherry (Prunus avium L.)

  2018cites this paper
• The target cells of anthocyanins in metabolic syndrome

  2018cites this paper
• Factors Affecting Quality and Health Promoting Compounds during Growth and Postharvest Life of Sweet Cherry (Prunus avium L.)

  2017cites this paper
• Blueberry as a source of bioactive compounds for the treatment of obesity, type 2 diabetes and chronic inflammation

  2017cites this paper
• Genotype, Environment and Management Practices on Red/ Dark-Colored Fruits Phenolic Composition and Its Impact on Sensory Attributes and Potential Health Benefits

  2017cites this paper
• The potential of flavonoids in the treatment of non-alcoholic fatty liver disease

  2017cites this paper
• Human paraoxonase 1 overexpression in mice stimulates HDL cholesterol efflux and reverse cholesterol transport

  2017cites this paper
• Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function.

  2017cites this paper
• Effects of Astaxanthin on Reverse Cholesterol Transport and Atherosclerosis in Mice

  2017cites this paper
• Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose–response randomised controlled trial

  2017cites this paper
• 1 PHYTOTHERAPIES — PAST , PRESENT , AND FUTURE

  2017cites this paper
• Anthocyanins in metabolic health and disease

  2017cites this paper
• Blueberries’ Impact on Insulin Resistance and Glucose Intolerance

  2016cites this paper
• Effects of Berries Consumption on Cardiovascular Risk Factors: A Meta-analysis with Trial Sequential Analysis of Randomized Controlled Trials

  2016cites this paper
• Emerging Potential of Natural Products as an Alternative Strategy to Pharmacological Agents Used Against Metabolic Disorders.

  2016cites this paper
• Evaluation of the effect of Vacciniumarctostaphylos L . fruit extract on serum inflammatory biomarkers in adult hyperlipidemic patients : a randomized double-blind placebo-controlled clinical trial

  2016cites this paper
• Iridoid-loganic acid versus anthocyanins from the Cornus mas fruits (cornelian cherry): Common and different effects on diet-induced atherosclerosis, PPARs expression and inflammation.

  2016cites this paper
• Evaluation of the effect of Vaccinium arctostaphylos L. fruit extract on serum inflammatory biomarkers in adult hyperlipidemic patients: a randomized double-blind placebo-controlled clinical trial

  2016cites this paper
• EFECTO HIPOLIPIDÉMICO DE LA CÁSCARA PULVERIZADA DE VITIS VINIFERA VARIEDAD PINOT NOIR (UVA BORGOÑA) EN RATAS CON HIPERLIPEMIA INDUCIDA

  2015cites this paper
• Recruited metastasis suppressor NM23-H2 attenuates expression and activity of peroxisome proliferator-activated receptor δ (PPARδ) in human cholangiocarcinoma.

  2015cites this paper
• PHYTOTHERAPIES—PAST, PRESENT, AND FUTURE

  2015cites this paper
• Chicory, a typical vegetable in Mediterranean diet, exerts a therapeutic role in established atherosclerosis in apolipoprotein E-deficient mice.

  2015cites this paper
• Retinoic acid induces macrophage cholesterol efflux and inhibits atherosclerotic plaque formation in apoE-deficient mice

  2015cites this paper
• Effects of phenol-enriched olive oils on HDL and endothelial functions in cardiovascular risk individuals

  2015cites this paper
• Impacts of Hibiscus esculentus extract on glucose and lipid profile of diabetic rats

  2015influential citation
• Consumption of polyphenol-rich peach and plum juice prevents risk factors for obesity-related metabolic disorders and cardiovascular disease in Zucker rats.

  2015cites this paper
• Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia.

  2014cites this paper
• Effect of Cosmos caudatus Kunth leaves on the lipid profile of a hyperlipidemia-induced animal model.

  2014cites this paper
• Optimization of Rutaecarpine as ABCA1 Up-Regulator for Treating Atherosclerosis.

  2014cites this paper
• Molecular mechanisms involved in the cardiovascular and neuroprotective effects of anthocyanins.

  2014cites this paper
• Evaluation of the Effects of Vaccinium arctostaphylos L. Fruit Extract on Serum Lipids and hs-CRP Levels and Oxidative Stress in Adult Patients with Hyperlipidemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

  2014cites this paper
• Biochemical and histopathological study of the anti-hyperglycemic and anti-hyperlipidemic effects of cornelian cherry (Cornus mas L.) in alloxan-induced diabetic rats

  2014cites this paper
• The protective effect of the Cornus mas fruits (cornelian cherry) on hypertriglyceridemia and atherosclerosis through PPARα activation in hypercholesterolemic rabbits.

  2014cites this paper
• Proanthocyanidins, anthocyanins and cardiovascular diseases

  2014cites this paper
• Green tea, cocoa, and red wine polyphenols moderately modulate intestinal inflammation and do not increase high-density lipoprotein (HDL) production.

  2014cites this paper
• Effects of Extracts of Unripe Black Raspberry and Red Ginseng on Cholesterol Synthesis

  2013cites this paper
• Wild blueberry (Vaccinium angustifolium)-enriched diet improves dyslipidaemia and modulates the expression of genes related to lipid metabolism in obese Zucker rats

  2013cites this paper
• Induction of peroxisome proliferator-activated receptor γ (PPARγ)-mediated gene expression by tomato (Solanum lycopersicum L.) extracts.

  2013cites this paper
• Tertiary-butylhydroquinone upregulates expression of ATP-binding cassette transporter A1 via nuclear factor E2-related factor 2/heme oxygenase-1 signaling in THP-1 macrophage-derived foam cells.

  2013cites this paper
• Pomegranate: a fruit that ameliorates metabolic syndrome.

  2013cites this paper
• Black rice anthocyanidins prevent retinal photochemical damage via involvement of the AP-1/NF-κB/Caspase-1 pathway in Sprague-Dawley Rats

  2013cites this paper
• Flavonoids as dietary regulators of nuclear receptor activity.

  2013cites this paper
• Olive oil polyphenols enhance the expression of cholesterol efflux related genes in vivo in humans. A randomized controlled trial.

  2013cites this paper
• Quercetin up-regulates expressions of peroxisome proliferator-activated receptor γ, liver X receptor α, and ATP binding cassette transporter A1 genes and increases cholesterol efflux in human macrophage cell line.

  2013cites this paper
• Functional Foods and Biotechnology

  2013cites this paper
• ffect of alcohol-free red wine concentrates on cholesterol omeostasis : An in vitro and in vivo study

  2013cites this paper
• Effect of alcohol-free red wine concentrates on cholesterol homeostasis: An in vitro and in vivo study

  2013cites this paper
• Dried Cherries: Phytochemicals and Health Perspectives

  2013cites this paper
• Cyanidin 3-O-β-d-glucoside-rich blackberries modulate hepatic gene expression, and anti-obesity effects in ovariectomized rats

  2012cites this paper
• Cyanidin-3-O-β-glucoside induces oxysterol efflux from endothelial cells: role of liver X receptor alpha.

  2012cites this paper
• Dietary resveratrol increases the expression of hepatic 7α-hydroxylase and ameliorates hypercholesterolemia in high-fat fed C57BL/6J mice

  2012influential citation
• Tanshinone II-A inhibits oxidized LDL-induced LOX-1 expression in macrophages by reducing intracellular superoxide radical generation and NF-κB activation.

  2012cites this paper
• Effects of Nutraceuticals and Botanicals on Macrophage Cholesterol Efflux: Implications for Atherosclerosis

  2012influential citation
• Is Coffee the Next Red Wine? Coffee Polyphenol and Cholesterol Efflux

  2012cites this paper
• Régulation du métabolisme et du transport des lipides dans les macrophages : potentiel anti-athérosclérotique des ligands du CD36

  2012cites this paper
• The Effects of 100% Tart Cherry Juice on Plasma Lipid Values and Markers of Inflammation in Overweight and Obese Subjects

  2012cites this paper
• Gut Microbiota Metabolism of Anthocyanin Promotes Reverse Cholesterol Transport in Mice Via Repressing miRNA-10b

  2012cites this paper
• Panax notoginseng saponins attenuate atherosclerosis via reciprocal regulation of lipid metabolism and inflammation by inducing liver X receptor alpha expression.

  2012cites this paper