Table 1.
In vitro and in vivo studies demonstrating the effect of oleocanthal, oleuropein, and hydroxytyrosol on markers of disease.
| Olive Oil Phenolic Treatment Concentration | Health/Disease Outcome | In Vitro/In Vivo Model | Key Findings | Reference |
|---|---|---|---|---|
| Oleocanthal (1–25 μM) |
Joint degenerative disease | Murine chondrocytes. In vitro |
Oleocanthal and its derivative 231 down-regulate iNOS protein expression in LPS-challenged chondrocytes reducing nitrate levels. | Iacono et al. (2010) [48] |
| Oleocanthal (50 μM) |
Joint degenerative disease | Murine chondrocytes, Murine macrophages In vitro |
Oleocanthal attenuates IL-6 and MIP- in vitro. The anti-inflammatory actions of oleocanthal in macrophages are related to the inhibition of NO production, via iNOS down regulation, and also to the decrease of relevant pro-inflammatory cytokines. | Scotece et al. (2013) [49] |
| Oleocanthal (10 nM) |
Neurodegenerative disease | Primary hippocampal cultures In vitro |
Oleocanthal alters the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs. | Pitt et al. (2009) [50] |
| Oleocanthal (100 μM) |
Neurodegenerative disease | Tau fibrils In vitro |
Oleocanthal inhibits tau fibrillization which is a risk factor for Alzheimer’s disease | Monti et al. (2011) [51] |
| Oleocanthal (100 μM) |
Neurodegenerative disease | Tau Fibrils In vitro |
Oleocanthal prevents fibrillization of tau by locking tau into the naturally unfolded state. | Li et al. (2009) [52] |
| Hydroxytyrosol (1–10 μM) |
Anti-inflammatory and anti-atherosclerotic activity | Human monocytic THP-1 cells In vitro |
Hydroxytyrosol blunts MMP-9 release and reduces COX-2 and NF-κB activation, suggesting a vascular protective effect. | Scoditti et al. (2014) [57] |
| Oleuropein (200 μg/mL) and hydroxytyrosol (50 μg/mL) |
Breast cancer | Human breast adenocarcinoma (MCF-7) cells In vitro |
Oleuropein and hydroxytyrosol decrease cell viability and inhibit cell proliferation, and induce cell apoptosis in breast cancer MCF-7 cells. | Han et al. (2009) [58] |
| Oleuropein (100μM) and hydroxytyrosol (50 μM) |
Breast cancer | SKBR3 BC cells. In vitro |
Oleuropein and hydroxytyrosol reduce breast cancer SKBR3 cell growth through the GPER pathway. | Chimento et al. (2014) [59] |
| Oleocanthal (25 μM) |
Breast cancer | Human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474, MDA-MB-231/GFP In vitro |
Oleocanthal reduce c-Met kinase activity, cell growth, migration, and invasion of breast cancer cells. | Akl et al. (2014) [60] |
| Oleocanthal (25, 50 μM ) |
Multiple myeloma | ARH-77 cells, human myeloma-derived cell line In vitro |
Oleocanthal inhibits MIP-1 expression and secretion in multiple myeloma cells and inhibits cell proliferation by inducing the activation of apoptosis mechanisms and by down-regulating ERK1/2 and AKT signal transduction pathways. | Scotece et al. (2013) [61] |
| Oleocanthal (20 Μm) |
Prostate and pancreatic cancer | PC3 (prostate), MDA-MB-231 (breast), and BxPC3 (pancreatic) cancer cells In vitro |
Oleocanthal induces cancer cell death by entering the lysosome and inhibiting ASM activity, which induces lysosomal membrane permeabilization. | LeGendre et al. (2015) [62] |
| Oleocanthal (10 μM) |
Malignant cutaneous melanoma | A375 human melanoma cell line. In vitro |
Oleocanthal has selective activity for human melanoma cells versus normal dermal fibroblasts as well inhibits ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. | Fogli et al. (2016) [63] |
| Oleocanthal (10 μM) |
Breast cancer | Human breast adenocarcinoma cell line MCF-7, human ductal breast epithelial tumor cell line T47D, human colorectal adenocarcinoma cell line Caco-2, human adenocarcinoma cell line and HeLa cell line. In vitro |
Oleocanthal inhibits the growth of breast cancer cell lines in a dose-dependent manner. Oleocanthal treatment produces down-regulation of phosphorylated mTOR in metastatic breast cancer cell line (MDA-MB-231). | Kanfar et al. (2015) [64] |
| Hydroxytyrosol (25 μM) |
Hyperlipidemia | C3H10 T1/2 adipocytes In vitro |
Hydroxytyrosol modifies genes related with adipocyte maturation and differentiation and inhibits lipid formation. | Warnke et al. [65] |
| Oleuropein (150 μM) Hydroxytyrosol (300 μM) |
Obesity | 3T3-L1 pre-adipocytes. In vitro |
Oleuropein and hydroxytyrosol act on 3T3-L1 cells to reduce 358 preadipocyte differentiation and lipid accumulation so may regulate the size of fat cells. | Drira et al. (2011) [66] |
| Hydroxytyrosol (1–20 μM) |
Obesity | Murine 3T3-L1 adipocytes, 3T3-L1 mouse embryo fibroblasts In vitro |
Hydroxytyrosol prevents adiponectin downregulation in inflamed adipocytes through an attenuation of JNK-mediated PPARγ suppression. | Scoditti et al. (2015) [67] |
| Oleuropein (50 μM) |
Atherosclerosis and tumor invasion. | Human monocyte-like cells In vitro |
Oleuropein inhibits MMP-9 expression and reduces invasiveness of tumor cells. | Dell’Agli et al. (2010) [46] |
| Oleocanthal (50 μM) |
Neurodegenerative disease | Bend3 cells Brain microvessels of C57BL/6 mice n = 6 In vivo |
Results from in vitro and in vivo studies demonstrate a consistent pattern of oleocanthal controlling Aβ levels and therefore reducing the risk of Alzheimer’s disease by enhancing Aβ clearance from the brain. | Abuznait et al. (2013) [53] |
| Hydroxytyrosol (4 mg/kg) |
Atherosclerosis | New Zealand rabbits (weight 2.5–3 kg) n = 8 In vivo |
Hydroxytyrosol improves antioxidant status and reduces the size of atherosclerotic lesions when compared with control animals suggesting that hydroxytyrosol may have cardioprotective effects | González-Santiago et al. (2006) [68] |
| Oleocanthal (30 μM) in vitro in vivo 5 mg/kg/d or 10 mg/kg/d for eight weeks |
Hepatocellular carcinoma | HCC cell lines (Huh-7, HepG2 and HCCLM3 BALB/c mice n = 6 In vivo |
Oleocanthal inhibits hepatocellular carcinoma tumor growth and metastasis by inactivating STAT3 both in vitro and in vivo. | Pei et al. (2016) [69] |
| Oleuropein (125 mg/kg of diet) |
Lung metastases | MCF-7 cells xenograft growth in ovariectomised mice n = 20 In vivo |
Oleuropein prevents both peripulmonary and parenchyma lung metastases. | Sepporta et al. (2014) [70] |
| Hydroxytyrosol (100, 250, 500 mg/kg) |
Inflammatory swelling and hyperalgesia | Male Sprague-Dawley rats n = 50. In vivo |
Hydroxytyrosol decreases pro-inflammatory cytokines IL-1β and TNF-α, reducing paw inflammation. | Gong et al. (2009) [55] |