Oleuropein: Health Benefits and Role in Preventing Non-Communicable Diseases

Oleuropein is best known for its blood pressure-lowering effect. When administered via intraperitoneal or intravenous injections, it significantly reduces systolic and diastolic blood pressure in animal models. The ability of oleuropein to lower blood pressure may justify the traditional use of olive leaf in the treatment of mild to moderate hypertension. Beyond hypertension, it has been shown to have cardioprotective, anti-inflammatory, antioxidant, anti-cancer, anti-angiogenic and neuroprotective functions, and thus may be of therapeutic potential for a variety of human disorders. Oleuropein reduces oxidative damage in the substantia nigra of aged rats, a region of the brain that is most affected by neurodegeneration in Parkinson's disease.

Oleuropein in the Anti-Diabetic Action of the Mediterranean Diet

It is now more than 50 years since the benefits of the Mediterranean diet on the prevention of cardiovascular and neurodegenerative diseases, cancers, and diet-related metabolic conditions, like diabetes, have been convincingly demonstrated. Diabetes is a major health problem in economically developed countries and is one of the leading causes of morbidity and mortality worldwide. In recent years, oleuropein has developed a growing interest in regard to the phenolic compounds contained in EVOO because of its broad metabolic effects. These effects might contribute to the benefits that are commonly seen in subjects who eat a Mediterranean diet. This narrative article has been written with the purpose of highlighting the possible metabolic benefits of oleuropein, with a specific focus on its effects on glucose metabolism and diabetes. Information was obtained by a PubMed/MEDLINE systematic search of articles that included oleuropein and diabetes as key words. Experimental data obtained in vitro and in animal studies and the results of clinical investigations are included and overviewed. This article will provide the readership with an update on the currently available evidence on this interesting compound and hopefully trigger further clinical research in order to develop better knowledge and to set the stage for its routine use.[1]

A Mediterranean dietary pattern is effective in managing nutrition-related metabolic disorders, including diabetes. Polyphenols are under the spotlight as they are compounds with greater biological interest among the nutraceuticals contained in the Mediterranean diet. Therefore, the potential of oleuropein, as a major component of EVOO in the Mediterranean diet for modulation of glucose metabolism, is rapidly gaining interest within the scientific community. Preclinical studies indicate that oleuropein improves glucose transport and intracellular metabolism, increases insulin sensitivity, and facilitates insulin secretion by pancreatic β-cells, thus supporting the intriguing hypothesis that this phenolic compound might be beneficial for the prevention of diabetes and control of hyperglycemia.  First, sources of it should be carefully defined by standardization of olive leaf extraction and purification procedures in order to have control of the administered amount that, up to now, has been extremely variable. Second, dose finding studies should be planned to define the threshold for oleuropein effects that may differ depending on the outcome of various interests. Third, appropriate assessment of the exposure time that is necessary to obtain biologically relevant effects will be needed. Finally, like any other dietary intervention, it would be useful to have laboratory tests that permit the definition of adherence to oleuropein use in chronic studies.

Olive-Derived Polyphenol Oleuropein on Human Health

Recently the beneficial effects of virgin olive oil have been ascribed to the content of polyphenols, which exert antioxidant, anti-inflammatory, anti-cancer, antimicrobial, antiviral, anti-atherogenic, hypoglycemic, hepatic-, cardiac- and neuro-protective effects. Virgin olive oil is consumed unrefined, and humans absorb a large part of the ingested olive oil phenols. Oleuropein, the molecule responsible for unprocessed olives characteristic bitter taste, is the most prevalent phenolic component in olive leaves, seed, pulp and peel of unripe olives (up to 14% of the dry weight); during fruit maturation, oleuropein undergoes hydrolysis, yielding different products, including hydroxytyrosol (2-(3,4-dihydroxyphenyl)ethanol). Beneficial effects of this medicine were also described with regard to heart damage, as demonstrated in isolated rat hearts subjected to 30 min of no-flow global ischemia and then reperfused. Data evidenced a reduction of creatine kinase and reduced glutathione release in the perfusate. Either the oxidized glutathione and the extent of lipid peroxidation were reduced, strengthening the hypothesis that it may exert antioxidant beneficial effects in the prevention of coronary heart disease. Olive-derived phenolic compounds, including oleuropein, can decrease the production of monocytic inflammatory mediators, decreasing the production of IL-1β in human whole blood cultures stimulated with monocytes-triggered by LPS.[2]

In support of the patent application, Hamdi et al. provide evidence collected using both the CAM (chick chorioallantoic membrane) assay, traditionally used to assess the anti-angiogenic property of various compounds to study neonatal angiogenesis, and an “Adult Mouse Ear Model” to study the effect of it associated with wound healing. In both models, after oleuropein treatment, they observed a reduction of the number of blood vessels, indicating this substance as an anti-angiogenic factor. Oleuropein was also indicated as a molecule with a therapeutic potential against Alzheimer’s disease. This medicine, in fact, has been described as a non-covalent binding molecule for amyloid-β (Aβ) 1–40 peptide. Olive oil and olive leaf extract are renowned natural traditional remedies used for the treatment of different conditions, including dermatitis, wound healing and treatment of burns, stomach and intestinal pain, malaria-induced fever, different infections, alopecia, rheumatic pain, otitis, rickets, distortions, sciatica, hypertension, as a diuretic, as a laxative and as an aphrodisiac.In light of the unique combination properties of oleuropein, it looks like we should “go back to the future” and continue to exploit this key dietary component of the Mediterranean diet to promote human health.

Oleuropein as an Agent in Non-Communicable Diseases

The great progress of medical research has highly contributed to decreased mortality due to severe pathologies. But, on the other hand, a longer life expectancy has been associated with a greater incidence of illness and disability. Oleuropein (Ole) is the major phenolic compound in the olive tree, Olea europaea L., and is particularly abundant in unprocessed olive fruit and leaves, with concentrations up to 140 mg g−1 on a dry matter basis in young olives, and 60–90 mg g−1 of dry matter in the leaves. In Olea europaea, Ole and oleoside 11-methyl ester are abundant secoiridoids whereas verbascoside is the main hydroxycinnamic derivative of olives. The evidence presented in this review demonstrates the several biological activities of oleuropein including antioxidant, anti-inflammatory and anticancer properties. Several epidemiological studies have reported a strict association between a diet rich in this polyphenol and the prevention of several NCDs, that are among the main causes of morbidity and mortality in the world.[3]

In conclusion, several in vitro and in vivo studies have demonstrated the ability of oleuropein to counteract oxidative stress and inflammation, to modulate the autophagy pathway, as well as to interfere in the amyloid aggregation process, suggesting its use, not only in the prevention, but also as a complementary therapy of some diseases. Despite the low bioavailabilty of oleuropein, some clinical trials reported several beneficial effects after administration of this compound, confirming the results obtained in vitro and in vivo studies. The effective daily dose of oleuropein to be administered in humans to achieve a theraputic effect is not known, but clinical and experimental evidence suggest that regular intake of this compound can be effective in the long term, representing a continuous low-intensity stimulus to the cellular defence against NCDs.

References

[1]Da Porto A, Brosolo G, Casarsa V, Bulfone L, Scandolin L, Catena C, Sechi LA. The Pivotal Role of Oleuropein in the Anti-Diabetic Action of the Mediterranean Diet: A Concise Review. Pharmaceutics. 2021 Dec 25;14(1):40. doi: 10.3390/pharmaceutics14010040. PMID: 35056936; PMCID: PMC8778910.

[2]Barbaro B, Toietta G, Maggio R, Arciello M, Tarocchi M, Galli A, Balsano C. Effects of the olive-derived polyphenol oleuropein on human health. Int J Mol Sci. 2014 Oct 14;15(10):18508-24. doi: 10.3390/ijms151018508. PMID: 25318054; PMCID: PMC4227229.

[3]Nediani C, Ruzzolini J, Romani A, Calorini L. Oleuropein, a Bioactive Compound from Olea europaea L., as a Potential Preventive and Therapeutic Agent in Non-Communicable Diseases. Antioxidants (Basel). 2019 Nov 22;8(12):578. doi: 10.3390/antiox8120578. PMID: 31766676; PMCID: PMC6943788.

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