Table 1.
In vitro studies that investigated the effects of HT at molecular levels.
| Study (year) | Sample | Treatment Groups | Methodology | Outcomes |
|---|---|---|---|---|
| [13] | Caco-2 cells (A) HAEC (B) |
A: HT 10, 15, 20, 25, 50 and 100 μmol/L B: 1, 2, 5 and 10 μM |
A: 21-day cultured cells with 24 h of HT incubation at different concentrations. B: HT or its metabolites and TNF- α or TNF-α alone among 24 h. |
HT reduced E-selectin, P-selectin, VCAM-1 and ICAM-1 at all doses compared with TNF-α alone. |
| [14] | HUVEC | HT and its metabolites 100 μM | HT or its metabolites exposure for 16 h. Then, cells were treated with TNF-α for 24 h. |
HT and sulfate metabolites suppressed the intracellular production of ROS. HT and all the metabolites can downregulated ICAM-1, VCAM-1 and E-selectin genes. |
| [15] | HUVEC HMEC-1 |
HT 0 μmol/L HT 1 μmol/L HT 10 μmol/L HT 30 μmol/L |
Increasing concentrations for 1 h. PMA stimulation. |
HT reduced the inflammatory markers: TNF-α, IL-1β, VCAM-1, ICAM-1. Lipid peroxide production was reduced too. SOD activity was rescued by HT treatment and ATP activity was increased. |
| [16] | HUVEC Raw264.7 cells |
HT 0–80 μM | HT were exposure alone at different concentrations and with acrolein. Cells were exposure to acrolein alone too. |
Suppression of phosphor–NF–kB, IL-1β, TNF- α and IL-6 while the expression of ABCA1 increased. |
| [17] | SGBS adypocytes | HT 1–10 μmol/L | Cells were exposure to HT 1 h before TNF-α stimulation. | Just 1 μmol/L of HT prevents the upregultated mRNA levels of MCP-1, CXCL-10, IL-1β, VEGF, COX-2 and MMP-2. 10 μmol/L prevented IL-6, ICAM-1 and MMP-9 mRNA upregulation too. |
| [19] | Caco-2 cells | HT 1 μM Tyr 1 μM Tyr Sulf 1 μM HT Sulf 1 μM HT Glu 1 μM Tyr Glu 1 μM |
LPS 1 μg/ml treatment + 72 h of incubation. Phenolic compounds’ pretreatment prior to LPS co-exposure for 48 h. |
Phenolic compounds’ pretreatment limits NO release and inhibited iNOS expression. |
| [21] | HUVEC | HT 0–160 μM | Increasing concentrations of HT for 24 and 48 h. | At low HT concentrations, wound healing and cell migration were improved. Tube formation was promoted too. |
| [22] | HUVEC and HREC | 10 ng/ml IL-1β 10 μM HT-30s + IL-1β |
Cells were treated with IL-1β w/o HT-30s every 24 h for 7 days. | HT treatment upregulated CD31 and FGFR1 gene expression while it downregulates α-SMA, Vimentin and TNF-β expression. It prevents SMAD 2/3 translocation too. |
| [18] | HUVEC | HT 10 μmol/L | Cells were exposure to HT 1 h before IL-1β stimulation among 3 h. | HT dowregulated VCAM-1, IL-1A and IL-1B target genes. |
| [23] | HAEC | 1–10 μM of HT-3G, HT-3S TYR-G, TYR-S and MeOH 100 μM of Apocynin and L-NNA |
Increasing concentrations of the compounds + 24 h incubation. Exposed to apocynin, L-NAA, the tested compounds or MeOH for 24 h. |
Phenolic compounds’ treatment decreased superoxide levels while it highly stimulate Akt1 activation. |
Abbreviations: ATP: Adenosine triphosphate; CD31: Cluster of differentiation 31-protein; FGFR1: Fibroblast growth factor receptor-1; Glu: Glucuronide; HAEC: Human Aortic Endothelial Cells; HMEC-1: Human Microvascular Endothelial Cell line; HREC: Human Retinal Endothelial Cells; HT: Hydroxytyrosol; HT-3Os: Hydroxytyrosol-3O sulfate; HUVEC: Human Umbilical Vein Endothelial Cells; ICAM-1: Intercellular adhesion molecule-1; IL-1β: Interleukin-1 β; iNOS: Inducible nitric oxide synthase; L-NNA: L-Nω-nitro-arginine; MeOH: Methanol; PMA: Phorbol myristate acetate; ROS: Reactive Oxygen Species; NO: Nitric oxide; SGBS: Simpson-Golabi-Behmel Syndrome; α-SMA: Smooth muscle actin; SOD: Superoxide dismutase; Sulf: Sulfate; TNF-α: Tumor Necrosis Factor- α; Tyr: Tyrosol; VCAM-1: Vascular cell adhesion molecule-1; VEGF: Vascular endothelial growth factor.