Protective Effect Of Hydroxytyrosol Research Articles

Hydroxytyrosol has a cardioprotective effect through dardarin and asprosin

IntroductionIn this investigation, we explored the potential involvement of dardarin (LRRK2) and asprosin in the protective efficacy of hydroxytyrosol (HT) against heart damage induced by corn syrup in rats.Material and methodsThe research was conducted at the Adıyaman University Experimental Research Center during the period from December 8, 2021, to July 12, 2023. Rats were categorized into four groups (<i>n</i> = 6) as follows: control, HT, corn syrup, and corn syrup + HT. Over a span of 6 weeks, rats were administered water infused with 30% corn syrup. Simultaneously, a 4 ml/kg/day solution containing HT was orally administered, both independently and in conjunction with corn syrup, throughout the 6-week period. The molecular parameters of LRRK2 and asprosin in the cardiac tissue were assessed through histopathological examination.ResultsIn this study, it was observed that the LRRK2 level increased and the asprosin level decreased in the control group as a result of administration of corn syrup. After HT treatment, the LRRK2 level decreased non-significantly, while the asprosin level increased significantly. No difference was seen in the HT-only group compared to the control.ConclusionsThe protective effect of HT against damage to the heart due to corn syrup consumption may be mediated by LRRK2 and asprosin.

Anti-neuroinflammatory effect of hydroxytyrosol: a potential strategy for anti-depressant development.

Introduction: Depression is a complex psychiatric disorder with substantial societal impact. While current antidepressants offer moderate efficacy, their adverse effects and limited understanding of depression's pathophysiology hinder the development of more effective treatments. Amidst this complexity, the role of neuroinflammation, a recognized but poorly understood associate of depression, has gained increasing attention. This study investigates hydroxytyrosol (HT), an olive-derived phenolic antioxidant, for its antidepressant and anti-neuroinflammatory properties based on mitochondrial protection. Methods: In vitro studies on neuronal injury models, the protective effect of HT on mitochondrial ultrastructure from inflammatory damage was investigated in combination with high-resolution imaging of mitochondrial substructures. In animal models, depressive-like behaviors of chronic restraint stress (CRS) mice and chronic unpredictable mild stress (CUMS) rats were examined to investigate the alleviating effects of HT. Targeted metabolomics and RNA-Seq in CUMS rats were used to analyze the potential antidepressant pathways of HT. Results: HT protected mitochondrial ultrastructure from inflammatory damage, thus exerting neuroprotective effects in neuronal injury models. Moreover, HT reduced depressive-like behaviors in mice and rats exposed to CRS and CUMS, respectively. HT's influence in the CRS model included alleviating hippocampal neuronal damage and modulating cytokine production, mitochondrial dysfunction, and brain-derived neurotrophic factor (BDNF) signaling. Targeted metabolomics in CUMS rats revealed HT's effect on neurotransmitter levels and tryptophan-kynurenine metabolism. RNA-Seq data underscored HT's antidepressant mechanism through the BDNF/TrkB signaling pathways, key in nerve fiber functions, myelin formation, microglial differentiation, and neural regeneration. Discussion: The findings underscore HT's potential as an anti-neuroinflammatory treatment for depression, shedding light on its antidepressant effects and its relevance in nutritional psychiatry. Further investigations are warranted to comprehensively delineate its mechanisms and optimize its clinical application in depression treatment.

Protective effect of hydroxytyrosol and tyrosol metabolites in LPS-induced vascular barrier derangement in vitro.

The maintenance of endothelial barrier function is essential for vasal homeostasis and prevention of cardiovascular diseases. Among the toxic stimuli involved in the initiation of atherosclerotic lesions, Gram negative lipopolysaccharide (LPS) has been reported to be able to trigger endothelial dysfunction, through the alteration of barrier permeability and inflammatory response. Hydroxytyrosol (HT) and tyrosol (Tyr), the major phenolic compounds of extra virgin olive oil (EVOO), as wells as their circulating sulphated and glucuronidated metabolites have been shown to exert anti-inflammatory effects at endothelial level. In this study we investigated the protective effects of HT and Tyr metabolites on LPS-induced alteration of permeability in Human Umbilical Vein Endothelial Cells (HUVEC) monolayers and examined underlying signaling pathways, focusing on tight junction (TJ) proteins, mitogen-activated protein kinase (MAPK) and NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. It was shown that LPS-increased permeability in HUVEC cells was due to the alteration of TJ protein level, following the activation of MAPK and NLRP3. HT and Tyr sulphated and glucuronidated metabolites were able to limit the effects exerted by LPS, acting as signaling molecules with an efficacy comparable to that of their precursors HT and Tyr. The obtained results add a further piece to the understanding of HT and Tyr metabolites mechanisms of action in vascular protection.

Liver Protection of Hydroxytyrosol Mediated by Spexin and TRPM2

Background/Aim: In the study, the role of Spexin (SPX) and TRPM2 in the protective effect of Hydroxytyrosol (HT) in rats given Corn Syrup was evaluated.
 Material and Method: The rats were divided into 4 groups (6 rats in each) (Control, HT, Corn Syrup, Corn Syrup +HT). Rats were given 30% Corn Syrup with drinking water for 6 weeks. 4 ml/kg/day liquid containing HT was applied by oral gavage alone and together with Corn Syrup for 6 weeks. Molecular parameters SPX and TRPM2 were examined histopathologically in liver tissue. 
 Results: The SPX levels decreased and the TRPM2 levels increased more in the Corn Syrup given Group than the Control Group. SPX levels increased and TRPM2 levels decreased after HT treatment. In the HT Group only, no differences were detected when compared to the control Group.
 Conclusion: SPX and TRPM2 may mediate the protective effect of HT on the liver in rats given corn syrup.

The protective effect of hydroxytyrosol on the heart in rats fed corn syrup: The role of spexin, pentraxin-3

Background/Aim: Increased consumption of corn syrup has been linked to various metabolic diseases. The Mediterranean diet, one of the healthiest known diets, is renowned for its cardioprotective effects. We investigated the possible roles of new molecules such as spexin (SPX) and pentraxin-3 (PTX-3) in the protective effect of hydroxytyrosol (HT), one of the primary main components of olive oil, in rats fed corn syrup. Methods: The animals were divided into four groups of n=6 rats each: Group I (Control), Group II (HT), Group III (Corn Syrup), and Group IV (Corn Syrup+HT). The rats were given 30% corn syrup with drinking water for 6 weeks. Liquid containing HT (4 ml/kg/day) was applied by oral gavage alone and together with corn syrup for 6 weeks. SPX and PTX-3 were examined histopathologically in the animals’ heart tissue after the rats were sacrificed, and histoscores were created for SPX and PTX-3 immunoreactivity. The data were analyzed using both one-way ANOVA and Tukey’s HSD test. Results: We detected a decrease in SPX (P<0.001) and an increase in PTX-3 (P=0.013) in the Corn Syrup group compared with the Control group. After HT treatment, an increase in SPX (P=0.025) and a decrease in PTX-3 (P<0.001) were detected. There were no differences between the HT and Control groups. Conclusion: The protective effects of HT against heart damage might be conferred via SPX and PTX-3. These molecules are considered to be important target molecules involved in the diagnosis and treatment of metabolic diseases.

Protective Effect of Hydroxytyrosol from Phyllanthus emblica Linn Leaves on Testicular Tissue Injury Induced by CS2 in Mice

Protective Effect of Hydroxytyrosol from Phyllanthus emblica Linn Leaves on Testicular Tissue Injury Induced by CS2 in Mice

Hydroxytyrosol protects against cisplatin-induced nephrotoxicity via attenuating CKLF1 mediated inflammation, and inhibiting oxidative stress and apoptosis

Cisplatin (CDDP) is widely used as a broad-spectrum anticancer chemotherapeutic drug, often giving rise to nephrotoxicity due to the enhancement of inflammation, oxidative stress, and apoptosis. Hydroxytyrosol (HT), a representative and effective polyphenol component of Fructus Ligustri lucidi, has been known to have anti-inflammatory and anti-oxidative effects. Chemokine-like factor 1 (CKLF1) is a novel chemokine participates in inflammation and related to various inflammatory diseases. The present study is to investigate the protective effects and mechanism of HT on CDDP injured HK-2 cells and kidneys of mice. HT protected HK-2 cells against CDDP toxicity, and improved CDDP-induced histopathalogical damage and renal dysfunction in mice. HT suppressed the increased expression of CKLF1 and NF-κB activation caused by CDDP, attenuating followed inflammatory response manifested by declined levels of TNF-α and IL-1β. The protective effects of HT against CDDP-induced injury were partly reversed on CKLF1 overexpressed HK-2 cells, which shown by decreased cell viability and increased activation of NF-κB. HT also up-regulated the activities of GSH and SOD decreased by CDDP, and inhibited the increased production of MDA and NO induced by CDDP. Moreover, HT also inhibited CDDP-induced apoptosis in kidneys of mice. Our results demonstrated that HT protected CDDP-induced renal injury through inhibiting CKLF1 mediated inflammatory pathway, and also by anti-oxidative stress and anti-apoptosis. HT may be an effective therapeutic agent in CDDP-induced nephrotoxicity.

Protective Effect of Hydroxytyrosol on LPS-Induced Inflammation and Oxidative Stress in Bovine Endometrial Epithelial Cell Line.

Bovine endometritis is a serious pathogen-induced infectious disease that affects the physiological processes of estrus, pregnancy and the postpartum condition. The inflamed endometrium responds by activating an inflammatory intracellular signaling cascade that leads to increased expression of proinflammatory cytokines and reactive oxygen species (ROS). Oxidative stress is closely related to several pathological conditions in perinatal dairy cows and play a key role in tissue damage. Hydroxytyrosol (HT), a natural phenolic alcohol with a strong antioxidant activity, displayed a wide range of biological effect. The aim of this study was to evaluate the protective effects of HT in an in vitro model of lipopolysaccharide (LPS)-induced inflammation in bovine uterine endometrial cells. Our results showed that HT had a significant protective effect in LPS-induced inflammation and oxidative stress. HT was also able to increase the capacity of endogenous antioxidant systems through the up-regulation of the NRF2 pathway. Furthermore, HT restored the tight junction protein expressions. In conclusion, our results showed the protective effects of HT in LPS-stimulated BEND cells. Therefore, the results of this study suggest an important protective role of HT in the treatment and prevention of uterine pathologies in dairy cows.

Effect of oxidative stress and 3-hydroxytyrosol on DNA methylation levels of miR-9 promoters.

Effect of oxidative stress and 3-hydroxytyrosol on DNA methylation levels of miR-9 promoters.

Protective effect of hydroxytyrosol and rosemary extract in a comparative study of the oxidative stability of Echium oil

The oxidative stability of Echium oil has been studied by two accelerated oxidation methodologies namely Rancimat and differential scanning calorimetry at selected temperatures in the range 50–110 °C. Kinetic analyses have provided Arrhenius parameters, oxidative stability indexes (OSI), temperature coefficients (tcoef), Q10 and OSI at 20 °C (OSI20) for both methodologies focussing on secondary and tertiary oxidation products. Peroxide, p-anisidine and polar compounds values have been measured to characterize from primary to tertiary oxidation products. In general, susceptibility of this oil to oxidation has been found to be larger than for other vegetable oils, according to the OSI20 values estimated by Rancimat and differential scanning calorimetry. However, the values of tcoeff and Q10 are found to be similar to those described for vegetable oils. In addition, a study of the influence of two antioxidants, namely hydroxytyrosol and rosemary extract on the oxidative stability of Echium oil has been carried out using both methodologies. Protective effects over oxidation by up to a threefold increase of OSI20 values have been found for both antioxidants at the highest dose utilized.

Protective effects of hydroxytyrosol against α-synuclein toxicity on PC12 cells and fibril formation

There is a considerable consensus that the increased production and/or aggregation of α-synuclein (αsyn) plays a central role in the pathogenesis of Parkinson's disease (PD). Therefore, a method of identifying molecules that block αsyn aggregation and prevent the loss of dopaminergic neurons is urgently needed in order to treat or slow the progression of PD. Hydroxytyrosol (HT), a well-known bioactive food compound present in olive oil, olives and wine, possesses demonstrated antioxidant and anti-inflammatory properties that can cross the Blood Brain Barrier (BBB). In the present work, the role of HT, tyrosol (TYR) and other tyrosine metabolites (hydroxyphenyl acetic acid (HPAA)) against αsyn aggregation, destabilisation and toxicity was evaluated through the use of different in vitro tests (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay). Results show that HT presents a strong inhibitory effect preventing αsyn aggregation and exercising a destabilising effect by disaggregating αsyn fibrils. Moreover, HT is able to counteract αsyn-induced toxicity. This is the first time that the effect of HT against αsyn toxicity and aggregation is evaluated. Thus, HT can be considered a promising compound for further approaches to tackling PD.

Protective Effect of Hydroxytyrosol Against Oxidative Stress Mediated by Arsenic-Induced Neurotoxicity in Rats.

The present study reports beneficial effect of hydroxytyrosol (HT) against arsenic (As)-induced oxidative stress in the rat brain. Rats were orally administered with sodium arsenite dissolved in distilled water (25ppm, by oral gavage) for 8weeks or HT (10mg/kg b. wt.) in combination with As. Results showed increase in protein oxidation and lipid peroxidation, while catalase and superoxide dismutase (SOD) activities as well as GSH content were decreased after As exposure in rat brain. Fourier transform infrared analysis showed significant alteration in peak area values that also validated the oxidative damage to lipids and proteins. In addition, As exposure caused increase in protein expression of caspase-3 and Bax, while Bcl-2 expression was downregulated resulting in translocation of cytochrome c from mitochondria to cytosol. Treatment of HT with As reversed protein oxidation, lipid peroxidation, and increased GSH content as well as catalase and SOD activities. Administration of HT also prevented translocation of cytochrome c from mitochondria and increased mitochondria/cytosol ratio of cytochrome c. Hence, treatment of HT with As improved antioxidant system and efficiently lowered the generation of oxidative stress in rat brain.

Hydroxytyrosol inhibits phosphatidylserine exposure and suicidal death induced by mercury in human erythrocytes: Possible involvement of the glutathione pathway

Hydroxytyrosol (HT) is a phenolic antioxidant naturally occurring in virgin olive oil. In this study, we investigated the possible protective effects of HT on programmed suicidal death (eryptosis) induced by mercury (Hg) treatment in intact human erythrocytes (RBC). Our study confirms that the Hg-eryptosis is characterized by phosphatidylserine (PS) exposure at the cell surface, with cell shrinkage and ATP and glutathione depletion; calcium influx is also a key event that triggers eryptosis. Here we report that cell preconditioning with an optimal dose (1–5 μM) of HT prior to exposure to 2.5 μM HgCl2 causes a noteworthy decrease in PS-exposing RBC, almost restoring ATP and GSH content. Conversely, HT shows no effect against decrease in cell volume nor against influx of extracellular calcium. Taken together our data provide the first experimental evidence of the efficacy of HT in modulating the programmed suicidal death in non nucleated cells; the reported findings also confirm that the prevention of Hg toxicity should be regarded as an additional mechanism responsible for the health-promoting potential of this dietary phenol. Finally, virgin olive oil would appear to be a promising healthy food to reduce the adverse effects of chronic mercury exposure in humans.

Protective effect of hydroxytyrosol and its predominant plasmatic human metabolites against endothelial dysfunction in human aortic endothelial cells

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in free and conjugated forms that may exert health benefits against atherosclerosis. The native form of HT is undetectable in plasma due to an extensive first pass phase II metabolism. Therefore, it is necessary to find strategies to obtain HT metabolites and to demonstrate their protective role against the endothelial dysfunction. Biosynthesis of the main plasmatic HT metabolites was performed through Caco-2 cells. The bioactivity of HT and the mixture of metabolites was tested at physiological concentrations (1, 2, 5, and 10 μM) in human aortic endothelial cells (HAEC) co-incubated with TNF-α (10 ng/mL) for 18 and 24 h. After the incubations, cells and media were analyzed to test possible deconjugation of metabolites or conjugation of HT. Both HT and metabolites significantly reduced the secretion of E-selectin, P-selectin, ICAM-1, and VCAM-1, but only HT metabolites further reduced MCP-1 at 24 h. HT underwent a conjugation process after incubation leading to its main metabolites in a dose-dependent manner. Physiological HT metabolites, synthetized for the first time by using an intestinal cell model, might be responsible in part for the protection against endothelial dysfunction.

The protective role of olive oil hydroxytyrosol against oxidative alterations induced by mercury in human erythrocytes

Hydroxytyrosol (HT) is a phenolic antioxidant naturally occurring in virgin olive oil. In this study, we investigated the possible protective effects of HT on the oxidative and morphological alterations induced by mercury (Hg) in intact human erythrocytes. These cells preferentially accumulate this toxic heavy metal. More importantly, Hg-induced echinocyte formation correlates with increased coagulability of these cells. Our results indicate that HT treatment (10–50 µM) prevents the increase in hemolysis and Reactive Oxygen Species (ROS) generation induced by exposure of cells to micromolar HgCl2 concentrations as well as the decrease in GSH intracellular levels. Moreover, as indicated by scanning electron microscopy, the morphological alterations are also significantly reduced by HT co-treatment. Taken together our data provide the first experimental evidence that HT has the potential to counteract mercury toxicity. The reported effect may be regarded as an additional mechanism underlying the beneficial cardio-protective effects of this dietary antioxidant, also endowed with significant anti-atherogenic and anti-inflammatory properties.

0158 : Effect of polyphenols of olive oil, hydroxytyrosol and its glucuronides on the vascular reactivity in a type 2 diabetes context

Hydroxytyrosol (HT) and Resveratrol (RES) are recognized as strong antioxidant polyphenolic compound. While RES antioxidative mechanisms are well known, those of HT are controversial because of its low intestinal absorption and its high metabolisation in glucuronides (GC), suggesting that these metabolites are susceptible to express HT biologicial activity in vivo . Our objective was to compare the vasorelaxant effect of Res, HT and GC on isolated aortic from young males Wistar rats (3months), old Wistar and GK rats (14 months), in presence or not of t -BOOH-induced oxidative stress (1mM; 30min). No vasorelaxant effect of the polyphenols was observed in young or old males Wistar rats. However, in old GK rats, Res and GC had significant vasorelaxant effect. In response to t -BOOH-induced oxidative stress, HT and RES protected the aortic rings of young Wistar rats (p < 0.05). However, different maximal relaxation was found between HT + t -BOOH, Res + t -BOOH and Control (72.5 ± 2.8%, 76.1% ± 7.7% vs 88.8 ± 0.7% ; p<0.05). The sensibility to Ach (EC50) was altered negatively in Res + t -BOOH and t -BOOH in comparison of Control (2084.6 ± 1687 nM, 2983.5 ± 1110 nM vs 66.9±10.7 nM). The protective effect of HT and RES against the acute effect of t -BOOH-induced oxidative stress in a normal context tends to confirm our results in old GK rats, highlighting an effect of these polyphenols only in a pro-oxidant context.

Protective effects of hydroxytyrosol on liver ischemia/reperfusion injury in mice

Hydroxytyrosol (HT), a main phenolic compound in olive oil, has been proved to be a potent antioxidant and has beneficial effects on health. However, the effect of HT on oxidative liver damage, as seen in ischemia/reperfusion (I/R) injury, is unknown. Here, we examined whether HT could protect liver against I/R injury. By using a mouse model, we found that HT administration protects against hepatic I/R injury, as indicated by the decreased levels of serum aminotransferase and less parenchymal necrosis and apoptosis. Serum levels of tumor necrosis factor-α, interleukin-6, macrophage inflammatory protein 2, as well as reactive oxygen species (ROS) content in liver tissues, were all decreased by HT, the latter correlated with the reduction of hepatic malondialdehyde (an index of oxidative stress) content and increased activities and expressions of liver antioxidant enzymes superoxide dismutase and catalase. The protective effect was also seen in isolated hepatocytes anoxia/reoxygenation assay. HT exerts protective effects against hepatic I/R injury in mice, which might be associated with its anti-oxidative, anti-inflammatory, and anti-apoptotic properties. HT may be an effective hepatoprotective agent and a promising candidate for the treatment of liver I/R injury.

The protective effects of hydroxytyrosol against ortho-phenylphenol-induced DNA damage in HepG2 cells

Ortho-phenylphenol (OPP) has been found to cause carcinomas in the urinary tract of rats. Since OPP is a potent genotoxic compound, and used as fungicides and antibacterial agents in fruits and fruit products, search for newer, better agents for protection against toxicity of OPP is required. In this study, the chemoprotective effect of hydroxytyrosol (HT) against OPP-induced DNA damage in HepG2 cells was investigated. Comet assay was used to detect the DNA damage induced by OPP. To elucidate the possible mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, intracellular generation of reactive oxygen species (ROS), and reduced glutathione (GSH). Results showed that HT significantly reduced the DNA strand breaks caused by OPP. Moreover, HT effectively suppressed OPP-induced ROS formation, and increased the GSH level. Lysosomal membrane and mitochondrial membrane were also protected when cells were pretreated with HT. These results suggested that the disruption of lysosomal membrane integrity and the oxidative stress, leading to DNA fragmentation, may be the mechanism of DNA damage induced by OPP. The antioxidant activity of HT may play an important part in attenuating the DNA damage of OPP.

Hydroxytyrosol, the phenolic compound of olive oil protects human PBMC against oxidative stress and DNA damage mediated by 2,3,7,8-TCDD

The protective effect of hydroxytyrosol (HT), a strong antioxidant compound from extra virgin olive oil, against TCDD induced toxicity was investigated in human peripheral blood mononuclear cells (PBMC). PBMC (1×106cellsmL−1) were divided into four groups and were incubated in a CO2 incubator (5% CO2) for 12h with vehicle, TCDD (10nM), TCDD+HT (10nM+100μM) and HT alone (100μM) respectively. To clarify the role of HT against TCDD induced cytotoxicity, oxidative stress and the levels of antioxidant enzymes were assessed. Incubation of PBMC with TCDD significantly decreased cell viability, catalase (CAT) and glutathione peroxidase (GPx) and increased the levels of superoxide dismutase (SOD), glutathione reductase (GR) and oxidative stress markers such as lipid peroxidation products (LPO), protein carbonyl content (PCC) and reactive oxygen species (ROS). Whereas, HT had an effective antioxidant property as observed by the increased cell viability, normalization of antioxidant enzymes and decreased levels of LPO, PCC and ROS in PBMC co-treated with HT and TCDD. Apoptosis detection and comet assay results shows that HT, by acting as an antioxidant, prevents the damage to DNA induced by TCDD. In addition light microscopic and histopathological observations revealed that the cells are apoptotic and degenerated during TCDD treatment, whereas cells showed intact morphology during co-treatment with HT. On the whole, the results reveal that HT exerts a promising antioxidant potential in protecting the PBMC against TCDD induced oxidative stress, which might be due to the presence of catechol moiety in its structure.

Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells

Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1α) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including γ-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1α led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress.