1. | Cerezo et al. 2019 [32] | To investigate the effects of serotonin, melatonin, 3-indoleacetic acid, 5-hydroxytryptophol and hydroxytyrosol (HT) on vascular endothelial growth factor (VEGF) activity. | Subject Human umbilical vein endothelial cells (HUVECs) induced with VEGF (25 ng/mL) for 5, 10 or 60 min. Treatment groups 1 µM of serotonin, melatonin, 3-indoleacetic acid, and 5-hydroxytryptophol each, as well as 50 µM of HT. | - 1.
Cell migration. - 2.
VEGF receptor 2 (VEGFR-2) phosphorylation. - 3.
PLCγ1, Akt and eNOS phosphorylation.
| - 1.
Serotonin and 5-hydroxytryptophol inhibited HUVEC migration by 97% and 50%, respectively. No result for melatonin and HT were reported. - 2.
All of the test compounds, whether alone or in combination, inhibits VEGFR-2 phosphorylation. - 3.
Only HT inhibits PLCγ1, while HT, melatonin and serotonin shared enhancement effect on Akt and eNOS.
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2. | Calabriso et al. 2018 [33] | To investigate the HT effects on endothelial dysfunction under inflammatory conditions. | Subject HUVECs induced with phorbol myristate acetate (PMA; 10 nmol/L). Treatment groups HT at 0, 1, 10, 30 µmol/L concentrations. | - 1.
mRNA levels of tumour necrosis factor-α (TNF-α) and interleukin-β (IL-1β). - 2.
mRNA levels of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1). - 3.
HUVEC cell migration. - 4.
HUVEC tube formation. - 5.
Mitochondrial and cytosolic reactive oxygen species (ROS) production. - 6.
Superoxide dismustase (SOD) activity and malondialdehyde (MDA) level. - 7.
Mitochodrial membrane potential. - 8.
Mitochondrial ATP synthase activity. - 9.
Protein and mRNA levels of ATP5β. - 10.
Protein and mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM).
| - 1.
HT attenuates PMA-induced upregulation of TNF-α and IL-1β. - 2.
HT attenuates PMA-induced upregulation of ICAM-1 and VCAM-1. - 3.
HT inhibits PMA-induced migration of HUVECs. - 4.
HT inhibits PMA-induced tube formation by HUVECs. - 5.
HT attenuates PMA-induced elevation of mitochondrial and cytosolic ROS level. - 6.
HT suppresses PMA-induced elevation of SOD activity and MDA level. - 7.
HT restores the PMA-induced depolarisation of the mitochondrial membrane potential. - 8.
HT restores the PMA-induced reduction of ATP synthase activity. - 9.
HT restores the PMA-induced downregulation of ATP5β. - 10.
HT restores the PMA-induced downregulation of PGC-1α and NRF-1, as well as the upregulation of TFAM.
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3. | Lopez et al. 2017 [34] | To investigate the effects of chemically synthesised metabolites (sulphate and glucuronate forms) from HT on oxidative stress and inflammation in TNF-α activated HUVECs. | Subject HUVECs induced with TNF-α. Treatment groups HT, HT sulfonate (HT-SUL), HT glucuronate (HT-GLU) at 0-200 µM concentrations. | - 1.
HUVEC cell viability. - 2.
ROS production Glutathione (GSH) level. - 3.
Gene expression of antioxidant enzymes glutathione peroxidase 1 (GPX1) and glutamate-cysteine ligase catalytic subunit (GCLC). - 4.
Gene and protein expression of HO-1. - 5.
Phosphorylation of IKKαβ, IκBα, and p65. - 6.
Gene and protein expression of adhesion molecules ICAM-1, VCAM-1, and E-selectin. - 7.
mRNA levels of, chemokine (CAC) motif ligand 2 (CCL2), prostaglandin-endoperoxidase synthase 2 (PTGS2).
| - 1.
HUVEC cell viability was not affected up to 100 µM concentrations of HT and its metabolite. - 2.
HT and HT-SUL suppress TNF-α-induced ROS formation. - 3.
HT and HT-SUL attenuates TNF-α suppression of GSH. - 4.
HT and HT-SUL attenuates TNF-α induced downregulation of GPX1 and GCLC. - 5.
HT and HT-SUL attenuates TNF-α induced downregulation of HO-1. - 6.
HT and all metabolites attenuate TNF-α induced phosphorylation of IKKαβ, IκBα, and p65. - 7.
HT and all metabolites suppress TNF-α induced upregulation of ICAM-1, VCAM-1 and E-selectin. - 8.
HT and all metabolites suppress TNF-α induced upregulation of CCL2 and PTGS2.
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4. | Cheng et al. 2017 [35] | To analyse the effects of HT on the proliferation and differentiation of human umbilical vein endothelial cells (HUVECs). | Subject HUVECs exposed to pulsed electromagnetic fields (PEMFs). Treatment groups HT at 0, 10, 30, 50, 100 and 150 μM concentrations. | - 1.
Cell proliferation. - 2.
Cell migration. - 3.
mRNA and protein levels of Akt, mTOR, TGF-β1, and p53.
| - 1.
HT enhances PEMF-induced HUVEC proliferation with 30 μM concentration resulted in the highest cell proliferation. - 2.
HT enhances PEMF-induced HUVEC cell migration compared with the control and PEMF treatment only. - 3.
Combination of HT and PEMF treatment elevated the mRNA and protein levels of Akt, mTOR and TGF-β1, but not p53 when compared to the control.
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5. | Zrelli et al. 2015 [36] | To evaluate the expression of HO-1 and NRF-2 in HT-induced endothelial wound healing. | Subject Porcine vascular endothelial cells (VECs). Treatment groups HT at 10, 30, 50 and 100 μM concentrations. | - 1.
mRNA levels of heme oxygenase 1 (HO-1). - 2.
Protein levels of HO-1 and NRF-2 following inhibition of PI3K, ERK and p38 signalling pathways. - 3.
Cell migration.
| - 4.
HT induced HO-1 mRNA expression in VECs. - 5.
HT induction of HO-1 and NRF-2 involves PI3K and ERK pathways, but not p38 the pathway. - 6.
HT increased VECs migration rate.
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6. | Zrelli et al. 2011 [37] | To study the effect of HT on proliferation and protection against oxidative stress-induced damage in VECs. | Subject Porcine VECs. Treatment groups HT at 10, 30, 50 and 100 μM concentrations. | - 1.
Cell proliferation, migration and protection against hydrogen peroxide (H2O2). - 2.
Phosphorylation of Akt, p38, and ERK1/2 kinase. - 3.
Cell proliferation and protection against H2O2 following inhibition of Akt, p38, and ERK1/2 pathways. - 4.
Nuclear NRF-2 protein levels following inhibition of Akt, p38, and ERK1/2 pathways. - 5.
Cell proliferation, migration and protection against H2O2 following inhibition of NRF-2. - 6.
mRNA and protein levels of HO-1 following inhibition of NRF-2. - 7.
Cell proliferation, migration and protection against H2O2 following inhibition of HO-1.
| - 1.
HT enhanced cell, migration and maintained VECs viability following H2O2 exposure. - 2.
50 µM HT phosphorylate Akt, p38, and ERK1/2 kinase. - 3.
Inhibition of Akt and ERK1/2, but not p38 impedes HT-induced cell proliferation and protection against H2O2. - 4.
Inhibition of Akt, p38, and ERK1/2 impedes HT-induced elevation of nuclear NRF-2 protein level. - 5.
Inhibition of NRF-2 impedes HT-induced cell proliferation, migration and protection against H2O2. - 6.
Inhibition of NRF-2 impedes HT-induced elevation of HO-1 mRNA and protein levels. - 7.
Inhibition of HO-1 impedes HT-induced cell proliferation, migration and protection against H2O2.
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7. | Avola et al. 2018 [38] | To investigate the effect of hydroxytyrosol on the irradiated light-emitting-diode-generated blue light (LED-BL) of human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs). | Subject HEKs (NCTC 2544) or HDFs irradiated with LED-BL. Treatment groups HT at 10, 25 and 50 µg/mL concentrations. | - 1.
Cell viability. - 2.
Reactive oxygen species (ROS) production. - 3.
DNA damage. - 4.
Gene and protein expression of MMP-1, MMP-12, collagen type I, and proliferating cell nuclear antigen (PCNA).
| - 1.
HT maintains both HEKs and HDFs viability following LED-BL irradiation. - 2.
HT reduced LED-BL-induced ROS production in both HEKs and HDFs. - 3.
HT reduced LED-BL-induced DNA damage in both HEKs and HDFs. - 4.
HT reverses LED-BL-induced increase in MMP-1, MMP-12 and PCNA, as well as the reduction in collagen I gene and protein levels in both HEKs and HDFs.
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8. | Meschini et al. 2018 [39] | To investigate the effects of olive vegetation waste (OVW) on lipopolysaccharide (LPS)-stimulated human THP-1 monocytes. | Subject Human THP-1 monocytes stimulated by LPS. Treatment groups OVW treated with immobilised tyrosinase (OVW-1), OVW treated with native tyrosinase (OVW-2), non-treated OVW (OVW-3). | - 1.
Compound content, particularly of HT. - 2.
Antioxidant activity. - 3.
DNA damage. - 4.
Cell cytotoxicity. - 5.
Cell apoptosis. - 6.
Cell proliferation. - 7.
Cell autophagy. - 8.
Protein expression of high mobility group box 1 (HMGB1) danger signal, granzyme B, IL-6, IL-1β and TNF-α.
| - 1.
HT content from highest to smallest were OVW-1, OVW-2 and OVW-3. - 2.
Antioxidant activity from highest to smallest were OVW-1, OVW-2 and OVW-3. - 3.
OVW-3 and OVW-1 reduced DNA damage with OVW-1 at 25 μg/mL showing the greatest reduction. - 4.
Cell viability was not affected by up to 50 μg/mL OVW-1. - 5.
OVW-1 at 50 µg/mL and 100 µg/mL induced apoptosis after 24 h and 48 h treatment. - 6.
Cell proliferation started to reduce at 50 µg/mL OVW-1. - 7.
OVW-1 at 25 µM promote cell autophagy. - 8.
OVW-1 inhibited the LPS-induced production of HMGB1, granzyme B, IL-6, IL-1β and TNF-α.
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9. | Guo et al. 2010 [40] | To investigate the effect of HT towards UVB-induced DNA damage in a human skin keratinocyte cell line, HaCaT | Subject HaCaT induced with UVB. Treatment groups HT: 0, 25, 50 and 100 µM | - 1.
DNA damage. - 2.
ROS production. - 3.
Oxidative stress. - 4.
Phosphorylation of NF-κB. - 5.
Phosphorylation of p53.
| - 1.
HT suppresses UVB-induced DNA damage. - 2.
HT suppresses UVB-induced ROS formation. - 3.
HT suppresses UVB-induced oxidative stress. - 4.
HT attenuates UVB-mediated NF-κB phosphorylation. - 5.
HT attenuates UVB-mediated p53 phosphorylation.
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10. | Jeon and Choi 2018 [41] | To evaluate the anti-inflammatory and antiaging effects of HT via UVA-induced aging model in HDFs. | Subject HDFs irradiated with UVA. Treatment groups HT: 5, 10, 20, 30 µM | - 1.
Cell viability. - 2.
Ratio of aged cells. - 3.
Gene expression of MMP-1, MMP-3, IL-1β, IL-6 and IL-8.
| - 1.
Cell viability was not affected up to 30 µM of HT. - 2.
HT decreased UVA-induced aged cells ratio. - 3.
HT decreased UVA-induced gene expression of MMPs, IL-1β, IL-6 and IL-8.
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11. | Ghalandari et al. 2018 [42] | To investigate the antimicrobial effect of HT, HT acetate (HTA) and HT oleate (HTO) on Staphylococcus aureus and Staphylococcus epidermidis. | Subject Staphylococcus aureus or Staphylococcus epidermidis Treatment groups HT, HTA or HTO at 3.125, 6.25, 12.5, 25, 50 and 100 mg/mL each. | - 1.
Minimum inhibitory concentration (MIC) for S. aureus. - 2.
Minimum bactericidal concentration (MBC) for S. aureus. - 3.
MIC for S. epidermidis. - 4.
MBC for S. epidermidis.
| - 1.
MIC were 3.125, 12.5 and 25 mg/mL for HT, HTA and HTO, respectively. - 2.
MBC were 6.25, 25, 50 mg/mL for HT, HTA and HTO, respectively. - 3.
MIC were 6.25, 12.5, 50 mg/mL for HT, HTA and HTO, respectively. - 4.
MBC were 12.5, 25 and 100 mg/mL for HT, HTA and HTO, respectively.
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12. | Medina-Martinez et al. 2016 [43] | To determine the antimicrobial activity of HT towards the growth of several bacteria strains | Subject 8 g-negative bacteria, namely, Erwinia carotovora, Klebsiella pneumonia, Pseudomonas aeruginosa, Yersinia enterocolitica, Salmonella thypimurium, Aeromonas hydrophila, Shigella sonnei, Escherichia coli and 4 g-positive bacteria, namely, Pediococcus acidilactici, Kocuria rhizophila, Listeria monocytogenes, and S. aureus. Further experiment with 4 strains of E. coli, namely, CECT 4972, CECT 516, CECT 553 and LFMFP 679. Treatment groups HT: 200, 400 and 1000 μg/mL | - 1.
MIC for the 12 test bacteria. - 2.
Growth kinetic for the four strains of E. coli. - 3.
HT stability.
| - 1.
MIC values were mostly equal or higher to 1000 μg/mL, except for S. aureus and E. coli which showed a MIC of 400 μg/mL. - 2.
HT at 200 and 400 reduced growth rate of all strains. HT at 1000 µg/mL inhibits the growth of all strains. - 3.
E. coli strains partly reduced HT levels supplemented to the culture media, but not significantly.
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13. | Crisante et al. 2015 [44] | To analyse the antioxidant and antibacterial activity of HT-based polyacrylate (HT-pAc) on S. epidermidis | Subject Staphylococcus epidermidis Treatment groups HT-pAc with concentrations of 1, 5 and 10 mg/mL | - 1.
Antioxidant activity. - 2.
MIC for S. epidermidis.
| - 1.
HT-pAc at 0.80 ± 0.02 mmol was required to achieve half the maximal antioxidative effect. - 2.
MIC value of HT-pAc for S. epidermidis is 2.5 mg/mL.
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