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Nutrients
2023 Mar 29;157:. doi: 10.3390/nu15071672.
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In Vitro Anti-Inflammatory and Vasculoprotective Effects of Red Cell Extract from the Black Sea Urchin Arbacia lixula.
Quarta S
,
Scoditti E
,
Zonno V
,
Siculella L
,
Damiano F
,
Carluccio MA
,
Pagliara P
.
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Sea urchins have emerged as an important source of bioactive compounds with anti-inflammatory and antioxidant properties relevant to human health. Since inflammation is a crucial pathogenic process in the development and progression of atherosclerosis, we here assessed the potential anti-inflammatory and vasculoprotective effects of coelomic red-cell methanolic extract of the black sea urchin Arbacia lixula in an in vitro model of endothelial cell dysfunction. Human microvascular endothelial cells (HMEC-1) were pretreated with A. lixula red-cell extract (10 and 100 μg/mL) before exposure to the pro-inflammatory cytokine tumor necrosis factor (TNF)-α. The extract was non-toxic after 24 h cell treatment and was characterized by antioxidant power and phenol content. The TNF-α-stimulated expression of adhesion molecules (VCAM-1, ICAM-1) and cytokines/chemokines (MCP-1, CCL-5, IL-6, IL-8, M-CSF) was significantly attenuated by A. lixula red-cell extract. This was functionally accompanied by a reduction in monocyte adhesion and chemotaxis towards activated endothelial cells. At the molecular level, the tested extract significantly counteracted the TNF-α-stimulated activation of the pro-inflammatory transcription factor NF-κB. These results provide evidence of potential anti-atherosclerotic properties of A. lixula red-cell extract, and open avenues in the discovery and development of dietary supplements and/or drugs for the prevention or treatment of cardiovascular diseases.
Figure 1. Effect of A. lixula extract on endothelial cell viability. HMEC-1 were treated with A. lixula extract for 4 h at the concentrations indicated, and then either treated with 10 ng/mL TNF-α or left untreated for 18 h. (A) Cell viability was assessed by the MTT assay and data (means ± S.D., n = 3) expressed as percent of unstimulated control. In (B), representative phase-contrast images (10× magnification) of cells after treatments are shown. (a) control; (b) TNF-α 10 ng/mL; (c) A. lixula extract 10 µg/mL + TNF-α; (d) A. lixula extract 100 µg/mL + TNF-α.
Figure 2. Effect of A. lixula extract on TNF-α-induced endothelial cell–monocyte adhesion. HMEC-1 were treated with A. lixula extract for 4 h at the concentration indicated, and then either treated with 10 ng/mL TNF-α or left untreated for 18 h. THP-1 were added to the HMEC-1 monolayers. Images of HMEC-1 and adherent THP-1 cells were visualized and counted (A). Data (means ± S.D., n = 3) are expressed as number of adherent monocytes per field. In (B), images captured with a phase contrast microscope (10× magnification) are shown. (a) control; (b) TNF-α 10 ng/mL; (c) A. lixula extract 10 µg/mL + TNF-α; (d) A. lixula extract 100 µg/mL + TNF-α. *** p < 0.001 vs. basal (untreated) control; ## p < 0.01 vs. TNF-α alone.
Figure 3. Effect of A. lixula extract on TNF-α-induced expression of endothelial adhesion molecules. HMEC-1 were treated with A. lixula extract for 4 h at the concentration indicated, and then either treated with 10 ng/mL TNF-α or left untreated for 18 h. (A) mRNA levels of VCAM-1 and ICAM-1 were measured by qPCR. Data (means ± S.D., n = 3) are expressed as fold induction over basal (untreated) control. *** p < 0.001 vs. basal (untreated) control; # p < 0.05 vs. TNF-α alone; ## p < 0.01 vs. TNF-α alone. (B) Endothelial cell surface protein expression of VCAM-1 and ICAM-1 was assessed by EIA and expressed as percent of TNF-α. *** p < 0.001 vs. basal (untreated) control; ## p < 0.01 vs. TNF-α alone.
Figure 4. Effect of A. lixula extract on TNF-α-induced expression of inflammatory genes in human endothelial cells. HMEC-1 were treated with A. lixula extract for 4 h at the concentration indicated, and then either treated with 10 ng/mL TNF-α or left untreated for 18 h. mRNA levels of MCP-1, CCL-5, IL-8 (A), IL-6, and M-CSF (B) were measured by qPCR. Data (means ± S.D., n = 3) are expressed as fold induction over basal (untreated) control. *** p < 0.001 vs. basal (untreated) control; # p < 0.05 vs. TNF-α alone; ## p < 0.01 vs. TNF-α alone; ### p < 0.001 vs. TNF-α alone.
Figure 5. Effect of A. lixula extract on TNF-α-induced chemiotaxis of monocytes. HMEC-1 were treated with A. lixula extract for 4 h at the concentration indicated, and then either treated with 10 ng/mL TNF-α or left untreated for 18 h. Culture medium was collected and added to the lower chamber of a Boyden chamber. THP-1 were added to the upper chamber. Migrated THP-1 cells were then measured by the MTT assay. Data (means ± S.D., n = 3) are expressed as percent of untreated control. ** p < 0.01 vs. basal (untreated) control; ## p < 0.01 vs. TNF-α alone.
Figure 6. Effect of A. lixula extract on TNF-α-induced NF-κB activation. HMEC-1 were treated with A. lixula extract for 4 h at the concentration indicated, and then either treated with 10 ng/mL TNF-α or left untreated for 1 h. Nuclear proteins were analyzed for NF-κB p65 DNA-binding activity by ELISA. Data (means ± S.D., n = 3) are expressed as percent of TNF-α. *** p < 0.001 vs. basal (untreated) control; ## p < 0.01 vs. TNF-α alone.
Ades,
HMEC-1: establishment of an immortalized human microvascular endothelial cell line.
1992, Pubmed
Ades,
HMEC-1: establishment of an immortalized human microvascular endothelial cell line.
1992,
Pubmed
Akita,
An Interleukin-6 Receptor Antibody Suppresses Atherosclerosis in Atherogenic Mice.
2017,
Pubmed
Anderson,
Distribution of spinochrome pigments in echinoids.
1969,
Pubmed
,
Echinobase
Apostolakis,
Interleukin 8 and cardiovascular disease.
2009,
Pubmed
Archana,
Nutrient composition and antioxidant activity of gonads of sea urchin Stomopneustes variolaris.
2016,
Pubmed
,
Echinobase
Artyukov,
Marine Polyhydroxynaphthoquinone, Echinochrome A: Prevention of Atherosclerotic Inflammation and Probable Molecular Targets.
2020,
Pubmed
,
Echinobase
Baker,
NF-κB, inflammation, and metabolic disease.
2011,
Pubmed
Blankenberg,
Adhesion molecules and atherosclerosis.
2003,
Pubmed
Boisvert,
A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice.
1998,
Pubmed
Braunersreuther,
A novel RANTES antagonist prevents progression of established atherosclerotic lesions in mice.
2008,
Pubmed
Braunersreuther,
Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice.
2007,
Pubmed
Calabriso,
Multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts: differential role of hydroxycinnamic acids, flavonols and stilbenes on endothelial inflammatory gene expression.
2016,
Pubmed
Castellano,
Anti-Inflammatory Activity of Marine Ovothiol A in an In Vitro Model of Endothelial Dysfunction Induced by Hyperglycemia.
2018,
Pubmed
,
Echinobase
Chamika,
In vitro characterization of bioactive compounds extracted from sea urchin (Stomopneustes variolaris) using green and conventional techniques.
2021,
Pubmed
,
Echinobase
Chi,
Interleukin-6 production by endothelial cells via stimulation of protease-activated receptors is amplified by endotoxin and tumor necrosis factor-alpha.
2001,
Pubmed
Cochran,
Interleukin-6 can prime THP-1 macrophages for enhanced production of tumor necrosis factor-alpha in response to LPS.
1992,
Pubmed
Collins,
P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects against atherosclerosis in apolipoprotein E-deficient mice.
2000,
Pubmed
Cybulsky,
Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis.
1991,
Pubmed
Cybulsky,
A major role for VCAM-1, but not ICAM-1, in early atherosclerosis.
2001,
Pubmed
de Villiers,
Macrophage phenotype in mice deficient in both macrophage-colony-stimulating factor (op) and apolipoprotein E.
1998,
Pubmed
Donia,
Management of oxidative stress and inflammation in cardiovascular diseases: mechanisms and challenges.
2021,
Pubmed
Ellulu,
Atherosclerotic cardiovascular disease: a review of initiators and protective factors.
2016,
Pubmed
Fedoreyev,
Antiviral and Antioxidant Properties of Echinochrome A.
2018,
Pubmed
,
Echinobase
Figtree,
A Call to Action for New Global Approaches to Cardiovascular Disease Drug Solutions.
2021,
Pubmed
Forman,
Targeting oxidative stress in disease: promise and limitations of antioxidant therapy.
2021,
Pubmed
Georgakis,
Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability.
2021,
Pubmed
Ghelani,
Anti-Inflammatory Effects of Compounds from Echinoderms.
2022,
Pubmed
,
Echinobase
Gu,
Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice.
1998,
Pubmed
Held,
Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial.
2017,
Pubmed
Hira,
Autofluorescence mediated red spherulocyte sorting provides insights into the source of spinochromes in sea urchins.
2020,
Pubmed
,
Echinobase
Hou,
In vitro antioxidant and antimicrobial activities, and in vivo anti-inflammatory activity of crude and fractionated PHNQs from sea urchin (Evechinus chloroticus).
2020,
Pubmed
,
Echinobase
Huber,
Interleukin-6 exacerbates early atherosclerosis in mice.
1999,
Pubmed
Huo,
Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions.
2000,
Pubmed
Hussain,
Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?
2016,
Pubmed
Ikeda,
Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner.
1991,
Pubmed
Jeong,
Echinochrome A protects mitochondrial function in cardiomyocytes against cardiotoxic drugs.
2014,
Pubmed
,
Echinobase
Jiao,
Polysaccharide Constituents of Three Types of Sea Urchin Shells and Their Anti-Inflammatory Activities.
2015,
Pubmed
,
Echinobase
Kähkönen,
Antioxidant activity of plant extracts containing phenolic compounds.
1999,
Pubmed
Kim,
Multifaceted Clinical Effects of Echinochrome.
2021,
Pubmed
,
Echinobase
Lee,
A new sulfonic acid derivative, (Z)-4-methylundeca-1,9-diene-6-sulfonic acid, isolated from the cold water sea urchin inhibits inflammatory responses through JNK/p38 MAPK and NF-κB inactivation in RAW 264.7.
2014,
Pubmed
,
Echinobase
Lennikov,
Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats.
2014,
Pubmed
,
Echinobase
Liang,
Marine Natural Products and Coronary Artery Disease.
2021,
Pubmed
Liberale,
Cytokines as therapeutic targets for cardio- and cerebrovascular diseases.
2021,
Pubmed
Lin,
Impact of MCP-1 in atherosclerosis.
2014,
Pubmed
Liu,
NF-κB signaling in inflammation.
2017,
Pubmed
Lutgens,
Gene profiling in atherosclerosis reveals a key role for small inducible cytokines: validation using a novel monocyte chemoattractant protein monoclonal antibody.
2005,
Pubmed
Madonna,
Relevance of new drug discovery to reduce NF-κB activation in cardiovascular disease.
2012,
Pubmed
Matranga,
Monitoring chemical and physical stress using sea urchin immune cells.
2005,
Pubmed
,
Echinobase
Mayer,
Marine pharmacology in 2009-2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action.
2013,
Pubmed
Medina-Leyte,
Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches.
2021,
Pubmed
Mestas,
Monocyte-endothelial cell interactions in the development of atherosclerosis.
2008,
Pubmed
Moreno-García,
Sea urchins: an update on their pharmacological properties.
2022,
Pubmed
,
Echinobase
Nageh,
Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice.
1997,
Pubmed
Neumann,
Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity.
1997,
Pubmed
Pagliara,
Chemical characterization of red cells from the black sea urchin Arbacia lixula by X-ray photoelectron spectroscopy.
2021,
Pubmed
,
Echinobase
Poston,
Expression of intercellular adhesion molecule-1 in atherosclerotic plaques.
1992,
Pubmed
Quarta,
Analysis of the Anti-Inflammatory and Anti-Osteoarthritic Potential of Flonat Fast®, a Combination of Harpagophytum Procumbens DC. ex Meisn., Boswellia Serrata Roxb., Curcuma longa L., Bromelain and Escin (Aesculus hippocastanum), Evaluated in In Vitro Models of Inflammation Relevant to Osteoarthritis.
2022,
Pubmed
Quarta,
Coffee Bioactive N-Methylpyridinium Attenuates Tumor Necrosis Factor (TNF)-α-Mediated Insulin Resistance and Inflammation in Human Adipocytes.
2021,
Pubmed
Ridker,
Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease.
2021,
Pubmed
Roth,
Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.
2020,
Pubmed
Rus,
Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall.
1996,
Pubmed
Scoditti,
Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKCα and PKCβ1 inhibition.
2014,
Pubmed
Shahidi,
Bioactivities of Phenolics by Focusing on Suppression of Chronic Diseases: A Review.
2018,
Pubmed
Shaposhnik,
Arterial colony stimulating factor-1 influences atherosclerotic lesions by regulating monocyte migration and apoptosis.
2010,
Pubmed
Shih,
Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells.
2020,
Pubmed
,
Echinobase
Sinha,
Local M-CSF (Macrophage Colony-Stimulating Factor) Expression Regulates Macrophage Proliferation and Apoptosis in Atherosclerosis.
2021,
Pubmed
Smith,
Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E.
1995,
Pubmed
Smith,
Echinoderm immunity.
2010,
Pubmed
,
Echinobase
Solís-Herruzo,
Interleukin-6 increases rat metalloproteinase-13 gene expression through stimulation of activator protein 1 transcription factor in cultured fibroblasts.
1999,
Pubmed
Stabili,
Screening of Three Echinoderm Species as New Opportunity for Drug Discovery: Their Bioactivities and Antimicrobial Properties.
2018,
Pubmed
,
Echinobase
von Hundelshausen,
RANTES deposition by platelets triggers monocyte arrest on inflamed and atherosclerotic endothelium.
2001,
Pubmed
Winter,
Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis.
2018,
Pubmed
Ylä-Herttuala,
Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions.
1991,
Pubmed
Zhang,
Role of TNF-alpha in vascular dysfunction.
2009,
Pubmed
