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Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells

Olive leaf extract (OLE) is used in traditional medicine as a food supplement and as an over-the-counter drug for a variety of its effects, including anti-inflammatory and anti-atherosclerotic ones. Mechanisms through which OLE could modulate these pathways in human vasculature remain largely unknow...

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Autores principales: Burja, Blaž, Kuret, Tadeja, Janko, Tea, Topalović, Dijana, Živković, Lada, Mrak-Poljšak, Katjuša, Spremo-Potparević, Biljana, Žigon, Polona, Distler, Oliver, Čučnik, Saša, Sodin-Semrl, Snezna, Lakota, Katja, Frank-Bertoncelj, Mojca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531989/
https://www.ncbi.nlm.nih.gov/pubmed/31157238
http://dx.doi.org/10.3389/fcvm.2019.00056
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author Burja, Blaž
Kuret, Tadeja
Janko, Tea
Topalović, Dijana
Živković, Lada
Mrak-Poljšak, Katjuša
Spremo-Potparević, Biljana
Žigon, Polona
Distler, Oliver
Čučnik, Saša
Sodin-Semrl, Snezna
Lakota, Katja
Frank-Bertoncelj, Mojca
author_facet Burja, Blaž
Kuret, Tadeja
Janko, Tea
Topalović, Dijana
Živković, Lada
Mrak-Poljšak, Katjuša
Spremo-Potparević, Biljana
Žigon, Polona
Distler, Oliver
Čučnik, Saša
Sodin-Semrl, Snezna
Lakota, Katja
Frank-Bertoncelj, Mojca
author_sort Burja, Blaž
collection PubMed
description Olive leaf extract (OLE) is used in traditional medicine as a food supplement and as an over-the-counter drug for a variety of its effects, including anti-inflammatory and anti-atherosclerotic ones. Mechanisms through which OLE could modulate these pathways in human vasculature remain largely unknown. Serum amyloid A (SAA) plays a causal role in atherosclerosis and cardiovascular diseases and induces pro-inflammatory and pro-adhesive responses in human coronary artery endothelial cells (HCAEC). Within this study we explored whether OLE can attenuate SAA-driven responses in HCAEC. HCAEC were treated with SAA (1,000 nM) and/or OLE (0.5 and 1 mg/ml). The expression of adhesion molecules VCAM-1 and E-selectin, matrix metalloproteinases (MMP2 and MMP9) and microRNA 146a, let-7e, and let-7g (involved in the regulation of inflammation) was determined by qPCR. The amount of secreted IL-6, IL-8, MIF, and GRO-α in cell culture supernatants was quantified by ELISA. Phosphorylation of NF-κB was assessed by Western blot and DNA damage was measured using the COMET assay. OLE decreased significantly released protein levels of IL-6 and IL-8, as well as mRNA expression of E-selectin in SAA-stimulated HCAEC and reduced MMP2 levels in unstimulated cells. Phosphorylation of NF-κB (p65) was upregulated in the presence of SAA, with OLE significantly attenuating this SAA-induced effect. OLE stabilized SAA-induced upregulation of microRNA-146a and let-7e in HCAEC, suggesting that OLE could fine-tune the SAA-driven activity of NF-κB by changing the microRNA networks in HCAEC. SAA induced DNA damage and worsened the oxidative DNA damage in HCAEC, whereas OLE protected HCAEC from SAA- and H(2)O(2)-driven DNA damage. OLE significantly attenuated certain pro-inflammatory and pro-adhesive responses and decreased DNA damage in HCAEC upon stimulation with SAA. The reversal of SAA-driven endothelial activation by OLE might contribute to its anti-inflammatory and anti-atherogenic effects in HCAEC.
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spelling pubmed-65319892019-05-31 Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells Burja, Blaž Kuret, Tadeja Janko, Tea Topalović, Dijana Živković, Lada Mrak-Poljšak, Katjuša Spremo-Potparević, Biljana Žigon, Polona Distler, Oliver Čučnik, Saša Sodin-Semrl, Snezna Lakota, Katja Frank-Bertoncelj, Mojca Front Cardiovasc Med Cardiovascular Medicine Olive leaf extract (OLE) is used in traditional medicine as a food supplement and as an over-the-counter drug for a variety of its effects, including anti-inflammatory and anti-atherosclerotic ones. Mechanisms through which OLE could modulate these pathways in human vasculature remain largely unknown. Serum amyloid A (SAA) plays a causal role in atherosclerosis and cardiovascular diseases and induces pro-inflammatory and pro-adhesive responses in human coronary artery endothelial cells (HCAEC). Within this study we explored whether OLE can attenuate SAA-driven responses in HCAEC. HCAEC were treated with SAA (1,000 nM) and/or OLE (0.5 and 1 mg/ml). The expression of adhesion molecules VCAM-1 and E-selectin, matrix metalloproteinases (MMP2 and MMP9) and microRNA 146a, let-7e, and let-7g (involved in the regulation of inflammation) was determined by qPCR. The amount of secreted IL-6, IL-8, MIF, and GRO-α in cell culture supernatants was quantified by ELISA. Phosphorylation of NF-κB was assessed by Western blot and DNA damage was measured using the COMET assay. OLE decreased significantly released protein levels of IL-6 and IL-8, as well as mRNA expression of E-selectin in SAA-stimulated HCAEC and reduced MMP2 levels in unstimulated cells. Phosphorylation of NF-κB (p65) was upregulated in the presence of SAA, with OLE significantly attenuating this SAA-induced effect. OLE stabilized SAA-induced upregulation of microRNA-146a and let-7e in HCAEC, suggesting that OLE could fine-tune the SAA-driven activity of NF-κB by changing the microRNA networks in HCAEC. SAA induced DNA damage and worsened the oxidative DNA damage in HCAEC, whereas OLE protected HCAEC from SAA- and H(2)O(2)-driven DNA damage. OLE significantly attenuated certain pro-inflammatory and pro-adhesive responses and decreased DNA damage in HCAEC upon stimulation with SAA. The reversal of SAA-driven endothelial activation by OLE might contribute to its anti-inflammatory and anti-atherogenic effects in HCAEC. Frontiers Media S.A. 2019-05-16 /pmc/articles/PMC6531989/ /pubmed/31157238 http://dx.doi.org/10.3389/fcvm.2019.00056 Text en Copyright © 2019 Burja, Kuret, Janko, Topalović, Živković, Mrak-Poljšak, Spremo-Potparević, Žigon, Distler, Čučnik, Sodin-Semrl, Lakota and Frank-Bertoncelj. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Burja, Blaž
Kuret, Tadeja
Janko, Tea
Topalović, Dijana
Živković, Lada
Mrak-Poljšak, Katjuša
Spremo-Potparević, Biljana
Žigon, Polona
Distler, Oliver
Čučnik, Saša
Sodin-Semrl, Snezna
Lakota, Katja
Frank-Bertoncelj, Mojca
Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells
title Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells
title_full Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells
title_fullStr Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells
title_full_unstemmed Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells
title_short Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells
title_sort olive leaf extract attenuates inflammatory activation and dna damage in human arterial endothelial cells
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531989/
https://www.ncbi.nlm.nih.gov/pubmed/31157238
http://dx.doi.org/10.3389/fcvm.2019.00056
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