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Hydroxytyrosol and its potential use in cardiovascular disease, cancer and AIDS

Views: 0     Author: Site Editor     Publish Time: 2023-01-17      Origin: Site

Hydroxytyrosol is the main phenolic component of olive oil. The authors' team reviewed the history of hydroxytyrosol research and, in addition to compositional studies, also reorganized and analyzed the mechanism of action of hydroxytyrosol, in cardiovascular disease, cancer, and acquired immunodeficiency syndrome (AIDSA).


Olive bitter glycosides and hydroxytyrosol

The value of olive oil, the soul of the Mediterranean diet, is mainly realized through its phenolic content, the most important of which is: hydroxytyrosol (2-(3,4-dihydroxyphenyl)-ethanol HOTYR). Early scholars believed that among the olive polyphenols, the one with the strongest in vitro antioxidant potential is hydroxytyrosol.

In addition, the ripening of olives is also importantly linked to hydroxytyrosol. The bitter taste of olives in general comes from olive bitter glycosides, which, as olives ripen, are enzymatically hydrolyzed into a non-glycosylated form: the glycosidic ligands of olive bitter glycosides, which are finally converted into hydroxytyrosol.


Potential use in cardiovascular disease

The importance of natural polyphenols for cardiovascular health has been confirmed by several studies that have focused on the active phenolic compounds present in virgin olive oil, particularly olive polyphenols and olive bitter glycosides, which have several anti-inflammatory and anti-atherogenic activities, such as: inhibition of LDL oxidation, platelet aggregation and other factors involved in the development of atherosclerosis.


1. Effects on endothelial dysfunction

Endothelial dysfunction induced by oxidative stress represents the initial stage of atherosclerotic lesion development.

Thus, the vessel wall of atherosclerotic patients contains high levels of reactive oxygen species (ROS), and these also affect several redox sensitivities in vascular cells, leading to migration and proliferation of vascular smooth muscle cells and affecting the expression of cell adhesion factors and chemokines, which in turn lead to chronic inflammation.

Therefore, reducing ROS levels, or increasing antioxidant capacity on top of existing ROS levels, has an important role in stopping the development of atherosclerosis.

HOTYR increases the cytosolic and nuclear protein level activity of the peroxidase Mrna, protein, and forkhead transcription factor 3a (FOXO3a), thereby directly increasing the expression of antioxidant enzymes, as well as the translocation of FOXO3a to the nucleus by phosphorylation of AMP-activated protein kinase (AMPK).

These findings suggest that HOTYR may regulate the antioxidant system in pulmonary artery endothelial cells (VEC) and prevent cardiovascular disease.

2. Protection of LDL from oxidative damage

The authors' team analyzed the efficacy of olive polyphenols, mainly HOTYR, in scavenging free radicals, regulating the expression of ligands of the human CD40 (a surface antigen related to T and B cell function) gene, reducing oxidized LDL in plasma and increasing urinary polyphenols, drawing on the scientific opinion published by the European Food Safety Authority (EFSA) in 2010 regarding polyphenols in olives.

These studies demonstrate the role of phenolic compounds as cholesterol (LDL) antioxidants, and it is on this basis that the EFSA panel concluded that 4mg of HOTYR and its derivatives from olives should be consumed daily, which means that at least 20g of olive oil is needed. In order to play a role in reducing the risk of atherosclerosis and provide a positive impact for patients with coronary heart disease.

3. Inhibit platelet aggregation

In addition to oxidative damage, platelet aggregation triggers thrombosis, which is also an important factor in the development of atherosclerotic lesions. Through a series of trials, the authors' team recognized that HOTYR can have an antithrombotic effect by reducing platelet coagulation, although the authors also stressed that this effect is not achieved by modulating cAMP and cGMP, but by reducing thromboxane B2, and that this effect must be based on the intake of extra virgin olive oil, not refined oil.

Also in another study, HOTYR and HOTYR-acetates and rat tests confirmed that the effect was similar to that of aspirin after 7 days of oral administration.


Potential and mechanisms of antitumor activity

The polyphenols in olive and olive oil products are heavily used to reduce the risk of several chronic diseases, and studies have confirmed that the source of this health benefit is the phenolic compounds, not the fatty acids.

Regarding cancer prevention activity, the authors' team believes that the current information has shown that HOTYR is able to inhibit the initiation and promotion/progression stages of cancer development by preventing the induction of DNA damage by toxic molecules from different genes and by inhibiting the proliferation and apoptosis of different tumor cells.

The authors' team reviewed data confirming that although HOTYR and olive bitter glucoside, like other antioxidants, achieve their regulatory effects through the production of hydrogen peroxide (H2O2), the data show that HL60 (human acute promyelocytic leukemia cells) incubated with HOTYR show apoptosis even under conditions that do not support H2O2 accumulation, meaning that in addition to H2O2 HOTYR has other mechanisms to antioxidate and promote apoptosis of undesirable cells. This explains why some of the trial data are negative: a significant decrease in normal ROS levels affects health.

Through the analysis of a large number of trials, the authors' team confirmed that HOTYR in cancer: anti-cancer cell proliferation, pro-apoptosis and anti-cancer cell invasion.

The authors concluded that the health benefits of polyphenols are mainly derived from their antioxidant and anti-inflammatory effects, as measured by an increase in the GSH/GSSG (glutathione reduced (GSH) to oxidative (GSSG) ratio, which indicates the oxidative and reductive state of cells) ratio and a decrease in lipid peroxidation levels in rat kidney tubular cells.

However, most of the above tests were performed in cell lines, while animal as well as human tests are rare, so further studies are needed to confirm the anti-tumor potential and mechanism of HOTYR.


Effects on human immunodeficiency virus

Acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by human immunodeficiency virus (HIV) infection.

There is no cure for HIV, only long-term anti-HIV therapy, but most of the drugs against HIV have chronic toxicity as well as drug resistance.

However, as of the publication of this article, HOTYR has gained widespread attention in the field of prevention of HIV infection and even alleviation of HIV-derived diseases due to its small molecule anti-inflammatory and antiviral properties.

The authors also revealed that the European Commission has funded a study that seeks to test the efficacy of HOTYR in preventing HIV infection, and it is expected that a biogel of the compound may be launched to prevent HIV transmission during sexual intercourse.

Summary: There is no clear information on the adverse effects of HOTYR. The authors' team did not give clear data on whether there would be adverse effects at acute doses or long-term administration, but did provide some experimental support, for example, in rat tests showing that there were no adverse effects in rats ingesting 500 mg/kg/day of hydroxytyrosol.

Toxicology evaluated clinical signs, grip strength, locomotor activity, food consumption, body weight, hematology, clinical biology, pathology, organ weights, and microscopic observations and found no toxicologically relevant effects.


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