# A Narrative Review of Metabolomic Insights into Olive Oil's Nutritional Value
## 2 Olive Oil Metabolomics
### Minor Compounds
#### Oleuropein  
The secoiridoid oleuropein (OLE) and its derivative hydroxytyrosol (HT) are two of the most important polyphenols, and their concentrations decrease during olive fruit maturation [13]. OLE exists at high concentrations in unprocessed olive leaves and olive fruit, whereas high concentrations of HT are present in olive fruit and olive oil [37]. OLE can protect cellular membranes against metal-induced lipid oxidation because of its ability to scavenge free radicals and chelate metals. Its antioxidant effect is evident from a reduction in the production of ROS and reactive nitrogen species (RNS) in in vitro cell-free systems. Furthermore, hydrogen peroxide-induced DNA damage is reduced when OLE is present, which stimulates the expression of intracellular antioxidant enzymes when cells are exposed to oxidative stress-inducing agents, such as angiotensin II [38]. In ethanol-induced oxidative stress, OLE enhances the levels of glutathione peroxidase (GPx-1), superoxide dismutase (SOD), and total glutathione (GSH) [39]. This suggests that OLE recruits antioxidant enzymes when the cell is exposed to oxidative stress caused by different compounds, thereby protecting against oxidative damage that could compromise several biomolecules. Moreover, the cardioprotective and hypotensive effects of OLE have been demonstrated in several studies [39; 40; 41; 42]. Administration of OLE resulted in decreased expression of enzymes that, when present at high levels, potentially indicate heart damage, such as lactate dehydrogenase (LDH) or alanine aminotransferase. In rabbits fed a high-cholesterol diet, OLE reduced LDL and cholesterol levels and increased ATP levels, indicating its cardio-protective effects [39]. A study examining the effects of OLE in rats with acute myocardial infarction found that the animals treated with OLE had lower levels of malondialdehydedehyde (MDA), IL-1B, TNF-\(\alpha\), creatine kinase-MB, troponin I, and LDH. Hence, treatment with OLE mitigates cardiac impairment because of its ability to alleviate oxidative stress and inhibit the release of proinflammatory cytokines [40]. A study conducted on human peripheral blood cells, in which OLE and HT were tested, showed that these two compounds have a protective role against oxidative DNA damage [41]. Among olive oil metabolites, OLE has shown cardioprotective effects against acute adriamycin cardiotoxicity and anti-ischemic and hypolipidemic activities. Indeed, the administration of a diet containing 7 mg/kg OLE reduced the total cholesterol and LDL oxidation levels in rabbits [42]. In rat models, the role of OLE in the reduction of oxidative stress was measured in ischemic hearts, relieving oxidized GSH and resulting in a reduction in oxidation-related damage [42]. Furthermore, olive leaf polyphenols have been shown to inhibit platelet function in vitro in the blood of 11 healthy, non-smoking males [43]. They produced significant dose-dependent suppression of ATP release by platelets and thus platelet aggregation. In addition, studies have highlighted how polyphenols, such as OLE, reduce cardiotoxicity induced by antineoplastic agents, such as doxorubicin, thereby inhibiting lipid peroxidation products and oxidative stress and reducing iNOS in cardiomyocytes. OLE also appears to promote the restoration of metabolic activity in stressed cardiomyocytes [44]. In addition, OLE seems to induce increased scavenger activity in hypertensive rats, acting on the expression of antioxidant factors such as SOD and at the molecular level for Nrf-2, leading to increased production of related antioxidative enzymes, nicotinamide adenine dinucleotide phosphate (NADPH) quinone dehydrogenase 1, and heme oxygenase-1. Furthermore, the activity of OLE against lipoxygenase (LOX) has been previously reported [45]. Nonetheless, OLE also has significant antidiabetic properties. Phenolic compounds can decrease the activity of digestive enzymes but can also inhibit glucose transporter 2 (GLUT2) in a dose-dependent manner.