TY  - JOUR
AU  - Burja, Blaz
AU  - Kuret, Tadeja
AU  - Janko, Tea
AU  - Topalović, Dijana
AU  - Živković, Lada
AU  - Mrak-Poljsak, Katjusa
AU  - Potparević, Biljana
AU  - Zigon, Polona
AU  - Distler, Oliver
AU  - Cucnik, Sasa
AU  - Sodin-Semrl, Snezna
AU  - Lakota, Katja
AU  - Frank-Bertoncelj, Mojca
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3344
AB  - 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-alpha in cell culture supernatants was quantified by ELISA. Phosphorylation of NF-kappa B 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-kappa B (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-kappa B 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 H2O2-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.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Cardiovascular Medicine
T1  - Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells
VL  - 6
DO  - 10.3389/fcvm.2019.00056
ER  - 

@article{
author = "Burja, Blaz and Kuret, Tadeja and Janko, Tea and Topalović, Dijana and Živković, Lada and Mrak-Poljsak, Katjusa and Potparević, Biljana and Zigon, Polona and Distler, Oliver and Cucnik, Sasa and Sodin-Semrl, Snezna and Lakota, Katja and Frank-Bertoncelj, Mojca",
year = "2019",
abstract = "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-alpha in cell culture supernatants was quantified by ELISA. Phosphorylation of NF-kappa B 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-kappa B (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-kappa B 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 H2O2-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.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Cardiovascular Medicine",
title = "Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells",
volume = "6",
doi = "10.3389/fcvm.2019.00056"
}

Burja, B., Kuret, T., Janko, T., Topalović, D., Živković, L., Mrak-Poljsak, K., Potparević, B., Zigon, P., Distler, O., Cucnik, S., Sodin-Semrl, S., Lakota, K.,& Frank-Bertoncelj, M.. (2019). Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells. in Frontiers in Cardiovascular Medicine
Frontiers Media Sa, Lausanne., 6.
https://doi.org/10.3389/fcvm.2019.00056

Burja B, Kuret T, Janko T, Topalović D, Živković L, Mrak-Poljsak K, Potparević B, Zigon P, Distler O, Cucnik S, Sodin-Semrl S, Lakota K, Frank-Bertoncelj M. Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells. in Frontiers in Cardiovascular Medicine. 2019;6.
doi:10.3389/fcvm.2019.00056 .

Burja, Blaz, Kuret, Tadeja, Janko, Tea, Topalović, Dijana, Živković, Lada, Mrak-Poljsak, Katjusa, Potparević, Biljana, Zigon, Polona, Distler, Oliver, Cucnik, Sasa, Sodin-Semrl, Snezna, Lakota, Katja, Frank-Bertoncelj, Mojca, "Olive Leaf Extract Attenuates Inflammatory Activation and DNA Damage in Human Arterial Endothelial Cells" in Frontiers in Cardiovascular Medicine, 6 (2019),
https://doi.org/10.3389/fcvm.2019.00056 . .