In vitro study of the blood-brain barrier transport of bioactives from Mediterranean foods.

The Mediterranean diet (MD), characterized by olive oil, olives, fruits, vegetables, and wine intake, is associated with a reduced risk of dementia. These foods are rich in bioactives with neuroprotective and antioxidant properties, including hydroxytyrosol (HT), tyrosol (TYRS), serotonin (SER) and protocatechuic acid (PCA), a phenolic acid metabolite of anthocyanins. It remains to be established if these molecules cross the blood-brain barrier (BBB), a complex interface that strictly controls the entrance of molecules into the brain. We aimed to assess the ability of tyrosine (TYR), HT, TYRS, PCA and SER to pass through the BBB without disrupting its properties. Using Human Brain Microvascular Endothelial Cells as an in vitro model of the BBB, we assessed its integrity by transendothelial electrical resistance, paracellular permeability and immunocytochemical assays of the adherens junction protein ß-catenin. The transport across the BBB was evaluated by ultra-high-performance liquid chromatography high resolution mass spectrometry. Results show that tested bioactives did not impair BBB integrity regardless of the concentration evaluated. Additionally, all of them cross the BBB, with the following percentages: HT (∼70%), TYR (∼50%), TYRS (∼30%), SER (∼30%) and PCA (∼9%). These results provide a basis for the MD neuroprotective role.

Hydroxytyrosol and dopamine metabolites: Anti-aggregative effect and neuroprotective activity against α-synuclein-induced toxicity.

The abnormal aggregation of the α-synuclein (αsyn) protein is involved in the formation of Lewy bodies in the brain of patients suffering from Parkinson disease (PD). Hydroxytyrosol (HT), a polyphenolic compound present in olives, olive oil, and wine, has been shown to inhibit aggregation and destabilise the αsyn aggregates, preventing neuronal cell death. However, very limited data have been published on the study of its metabolites. Therefore, this study investigated the capacity of the metabolites 3,4-dihydroxyphenylacetaldehyde (DOPAL), 4-hydroxy-3-methoxyphenylethanol (MOPET), and 3-methoxy-4-hydroxyphenylacetaldehyde (MOPAL) to prevent the aggregation and toxic effects of αsyn fibrils. In vitro techniques, such as Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis, thiazolyl blue tetrazolium bromide (MTT), and Real-Time PCR (RT-PCR) were used. Our results show that among these three metabolites, DOPAL exerts the greatest effect, preventing aggregation and αsyn-induced neurotoxicity. In fact, DOPAL has the ability to completely inhibit αsyn fibril formation at low doses. Moreover, this metabolite has a potent destabilising effect on the αsyn fibrils. Concerning neuroprotection, DOPAL can counteract the toxicity induced by αsyn. The vitagene expression results show a possible relationship between the neuroprotection mechanism exhibited by DOPAL and the modulation of SIRT-2 and Hsp70.

Hydroxytyrosol in Foods: Analysis, Food Sources, EU Dietary Intake, and Potential Uses.

Hydroxytyrosol (HT) is a phenolic compound with proven biological properties present in a limited number of foods such as table olives, virgin olive oil (VOO) and wines. The present work aims to evaluate the dietary intake of HT in the European (EU) population by compiling scattered literature data on its concentration in foods. The consumption of the involved foods was estimated based on the EFSA Comprehensive European Food Consumption Database. The updated average contents of HT are as follows: 629.1, 5.2 and 2.1 µg/g for olives, olive oil and wine, respectively. The HT estimated intake in the European Union (EU) adult population falls within 0.13-6.82 mg/day/person, with table olives and wine being the main contributors. The estimated mean dietary intake of HT in EU countries is 1.97 ± 2.62 mg/day. Greece showed the highest HT intake (6.82 mg/day), while Austria presented the lowest (0.13 mg/day). Moreover, HT is an authorized novel food ingredient in the EU that can be added to different foods. Since the estimated HT intake is substantially low, the use of HT as a food ingredient seems feasible. This opens new possibilities for revalorizing waste products from olive oil and olive production which are rich HT sources.

Short-Term Pilot Study to Evaluate the Impact of Salbi Educa Nutrition App in Macronutrients Intake and Adherence to the Mediterranean Diet: Randomized Controlled Trial.

Promoting a healthy diet is a relevant strategy for preventing non-communicable diseases. This study aims to evaluate the impact of an innovative tool, the SAlBi educa nutrition app, in primary healthcare dietary counseling to improve dietary profiles as well as adherence to the Mediterranean diet. A multi-center randomized control trial comprising 104 participants was performed. Both control (n = 49) and intervention (n = 55) groups attended four once-weekly sessions focusing on healthy eating habits and physical activity, over one month. As well as attending the meetings, the intervention group used the app, which provides self-monitoring and tailored dietary advice based on the Mediterranean diet model. In a second intervention (one arm trial), the potential of SAlBi educa was evaluated for three months during the COVID-19 pandemic. At 4 weeks, the intervention group had significantly increased their carbohydrate intake (7.7% (95% CI: 0.16 to 15.2)) and decreased their total fat intake (-5.7% (95% CI: -10.4 to -1.15)) compared to the control group. Significant differences were also found for carbohydrates (3.5% (95% CI: -1.0 to 5.8)), total fats (-5.9% (95% CI: -8.9 to -3.0)), fruits and vegetables (266.3 g/day (95% CI: 130.0 to 402.6)), legumes (7.7g/day (95% CI: 0.2 to 15.1)), starchy foods (36.4 g/day (95% CI: 1.1 to 71.7)), red meat (-17.5 g/day (95% CI: -34.0 to -1.1)), and processed meat (-6.6 g/day (95% CI: -13.1 to -0.1)) intakes during the COVID-19 pandemic. SAlBi educa is a useful tool to support nutrition counseling in primary healthcare, including in special situations such as the COVID-19 pandemic. Trial registration: ISRCTN57186362.

SAlBi educa (Tailored Nutrition App for Improving Dietary Habits): Initial Evaluation of Usability.

In recent years, the use of applications to improve dietary habits has increased. Although numerous nutrition apps are available on the market, only few have been developed by health and nutrition professionals based on scientific evidence and subsequently tested to prove their usability. The main objective of this study was to design, develop, and evaluate the usability of a tailored nutrition application to be used to promote healthy eating habits. In order to decide app design and content, three focus groups took place with fifteen professionals from primary healthcare, nutrition, and food science and computer science, as well as expert users. For the general and feedback message design, a reference model based on the scientific literature was developed. To address the multi-perspective approach of users' and external healthcare professionals' feedback, a one-day pilot testing with potential users and healthcare professionals was conducted with four focus groups. To evaluate the relevance and potential usability of the app a 1-month pilot test was conducted in a real-life environment. A total of 42 volunteers participated in the one-day pilot testing, and 39 potential users participated in the 1-month pilot test. The SAlBi educa app developed includes an online dietary record, a self-monitoring tool to evaluate dietary patterns, general and feedback messages, and examples of traditional Mediterranean recipes. The usability study showed that volunteers think that SAlBi educa is pleasant (59%) and easy to learn to use (94%). Over 84% of the volunteers declared that the nutritional messages were clear and useful. Volunteers stated that general and tailored recommendations, as well as self-monitoring, were SAlBi educa's most motivating and useful features. SAlBi educa is an innovative, user-friendly nutritional education tool with the potential to engage and help individuals to follow dietary habits based on the Mediterranean model.

Anti-VEGF Effect of Bioactive Indolic Compounds and Hydroxytyrosol Metabolites.

Angiogenesis is a key process involved in both cancer and cardiovascular diseases, the vascular endothelial growth factor (VEGF) and its VEGF receptor-2 (VEGFR-2) being the main triggers. The aim of this study was to determine the molecular mechanism underlying the potent inhibition of VEGF signaling by hydroxytyrosol (HT) metabolites and indolic compounds and establish a relation between their structure and bioactivity. Experiments involved the evaluation of their potential to inhibit VEGF on human umbilical vein endothelial cells (HUVECs) by ELISA assay and their subsequent effect on the downstream signaling pathway (PLCγ1, Akt, and endothelial nitric oxide synthetase (eNOS)) by Western blot. Respectively, 3,4-dihydroxyphenylacetaldehyde (DOPAL) (100 µM) and indole pyruvic acid (IPy) (1 mM) were capable of inhibiting VEGFR-2 activation with an IC50 value of 119 µM and 1.037 mM. The anti-angiogenic effect of DOPAL and IPy is mediated via PLCγ1. Additionally, DOPAL significantly increases eNOS phosphorylation, while IPy maintained it. These data provide for the first time evidence of the anti-angiogenic effect of DOPAL and IPy for future use as potential bioactive food ingredients.

Occurrence of melatonin and indolic compounds derived from l-tryptophan yeast metabolism in fermented wort and commercial beers.

Melatonin and serotonin are bioactive compounds present in foods and beverages and related to neuroprotection and anti-angiogenesis, among other activities. They have been described in wines and the role of yeast in their formation is clear. Thus, this study evaluates the content of these bioactives and other related indolic compounds in beer. For this purpose, commercial beers were analyzed by a validated UHPLC-HRMS method and sample treatment optimized due to the low concentrations expected. Moreover, a wort was fermented with different commercial beer yeast (Abbaye, Diamond, SafAle, SafLager) in order to monitor the formation of these bioactives during the elaboration process. Results show that indolic compounds such as N-acetylserotonin and 3-indoleacetic acid are produced during the alcoholic fermentation of wort. Moreover, the occurrence of four indolic compounds (5-hydroxytryptophan, N-acetylserotonin, 3-indoleacetic acid, l-tryptophan ethyl ester) in commercial beers is reported for the first time.

Anthocyanins in Blueberries Grown in Hot Climate Exert Strong Antioxidant Activity and May Be Effective against Urinary Tract Bacteria.

Anthocyanins are extensively studied for their health-related properties, including antibacterial activity against urinary tract infections (UTI). Among common fruits, blueberries, with their remarkable antioxidant capacity, are one of the richest sources. Anthocyanin-rich extracts were obtained from four varieties: Snowchaser, Star, Stella Blue and Cristina Blue, grown in the hot climate of Southern Spain. Their total anthocyanins contents (TAC) were determined spectrophotometrically, and the anthocyanin profile by ultra high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS). Their antioxidant activity was assessed by oxygen radical absorbance capacity (ORAC) assay, while antibacterial activity against strains isolated from UTI patients was assessed in vitro, helping to select the varieties with the highest bioactive potential. Star showed the highest TAC and antioxidant activity (1663 ± 159 mg of cyanidin-3-O-glucoside (cy-3-O-glu) equivalents/100 g fresh weight (FW), 6345 ± 601 µmol Trolox equivalents (TE)/100 g FW, respectively), followed by Cristina Blue, Stella Blue and Snowchaser. As far as we know, this is the first time that cyanidin-3-rutinoside has been identified in blueberries. The extracts inhibited all the tested strains, MICs ranging from 0.4 mg/mL (for Stella Blue extract against UTI P. aeruginosa) to 9.5 mg/mL (for all extracts against UTI K. pneumoniae ssp. pneumoniae). This is the first study that assessed in vitro the antibacterial activity of blueberries against Klebsiella pneumoniae, Providencia stuartii and Micrococcus spp. strains isolated from UTI.

Chemical hazards in grapes and wine, climate change and challenges to face.

Climate change has an impact on the chemical risks associated to wine consumption related with grape development and microbial contamination. We can classify chemical hazards in wine into two groups: those present in grapes due to agricultural practices, environmental contamination or fungal growth and those coming from fermentation and the winemaking process. The first group includes mycotoxins, whilst the second encompasses ethyl carbamate, biogenic amines, sulfur dioxide and proteins used as technological ingredients such as fining material. Usually the effective control of chemical hazards is achieved by assuring that they either are minimized or absent in the final product since their removal is somewhat difficult and sometimes it may affect sensory properties, which is a major issue in wine. Interestingly, it is possible to give recommendations to avoid excess of these compounds, but more research is needed to face future challenges related to climate change and consumer demands.

Anti-VEGF Signalling Mechanism in HUVECs by Melatonin, Serotonin, Hydroxytyrosol and Other Bioactive Compounds.

Angiogenesis drives evolution and destabilisation of atherosclerotic plaques and the growth and expansion of tumour cells. Vascular endothelial growth factor (VEGF) is the main endogenous pro-angiogenic factor in humans. The aim was to provide insight into the anti-VEGF activity of bioactive compounds derived from aromatic amino acids (serotonin, melatonin, 3-indoleacetic acid, 5-hydroxytryptophol and hydroxytyrosol). Experiments involved endothelial cell migration (wound-healing assay), the molecular mechanisms (ELISA assay) and the downstream effects (phospholipase C gamma 1 (PLCγ1), protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) by Western blot) on human umbilical vein endothelial cells (HUVECs). The data suggest for the first time that hydroxytyrosol interacts with surface components of the endothelial cell membrane (, preventing VEGF from activating its receptor. Serotonin and 5-hydroxytryptophol significantly inhibited HUVEC migration (98% and 50%, respectively) following the same mechanism. Conversely to other bioactive compounds, the anti-angiogenic effect of melatonin, serotonin, 3-indoleacetic acid and 5-hydroxytryptophol is not mediated via PLCγ1. However, hydroxytyrosol inhibits PLCγ1 phosphorylation. Additionally, melatonin and serotonin maintained eNOS phosphorylation and hydroxytyrosol significantly activated eNOS-all via Akt. These data provide new evidence supporting the interest in melatonin, serotonin, 3-indoleacetic acid, 5-hydroxytryptophol and hydroxytyrosol for their further exploitation as anti-VEGF ingredients in food.

Melatonin, protocatechuic acid and hydroxytyrosol effects on vitagenes system against alpha-synuclein toxicity.

Preventing the abnormal assembly of α-synuclein (α-Syn) and the correct modulation of vitagenes system exercise strong neuroprotective effects. It has been reported that melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT) reduce α-Syn toxicity. Their effect on the vitagenes system of PC12 cells have not been explored yet. These bioactive can cross the blood brain barrier (BBB). Therefore, this work aims to evaluate the inhibitory and destabilising capacities of MEL, PCA, HT, and their combinations on α-Syn kinetics and effects on vitagenes system (sirtuin-1 (SIRT-1), sirtuin-2 (SIRT-2), heme oxygenase (HO-1) and heat shock protein 70 (Hsp-70)). In vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis, MTT assay and qPCR) were used. Compounds, both individually and simultaneously were able to decrease the toxicity induced by α-Syn. Concurrently, occurrence of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilisation of α-Syn fibrils (88 and 62%, respectively). Moreover, these compounds increased the expression of SIRT-2, HO-1 and Hsp70, contributing to a neuroprotective effect. In addition, the most important result is the increase on the expression of SIRT-2 caused by the combination of MEL + HT + PCA in the absence of α-Syn fibrils.

Palm Oil on the Edge.

Internationally recognized Spanish experts in the food industry, nutrition, toxicology, sustainability, and veterinary science met in Madrid on July 2018 to develop a consensus about palm oil (PO) as a food ingredient. Their aim was to provide a useful, evidence-based point of reference about PO. Scientific evidence about the role of PO in food safety, nutrition and sustainability was analyzed. Main conclusions were: (1) RSPO foundation responded to the environmental impact of palm crops. The Amsterdam Declaration pursues the use of 100% sustainable PO in Europe by 2020. Awareness about choosing sustainable products will help to maintain local economies and environments in the producing countries; (2) evidence shows that a moderate intake of PO within a healthy diet presents no risks for health. No evidence justifies any change fat intake recommendations; (3) food industry is interested in assuring safe, sustainable and high-quality products. The use of certified sustainable PO is increasing; and (4) there is no evidence associating PO consumption and higher cancer risk, incidence or mortality in humans. Tolerable daily intake (TDI) for toxic contaminants (2-and 3-monochloropropanediols (MCPDs), glycidyl esters (GEs)) have been established by JECFA and EFSA. Consequently, the European Commission has modified the Contaminants Regulation for GEs and it is still working on 3-MCPDs'.

Saccharomyces cerevisiae and Torulaspora delbrueckii Intra- and Extra-Cellular Aromatic Amino Acids Metabolism.

Tryptophan, phenylalanine, and tyrosine play an important role as nitrogen sources in yeast metabolism. They regulate biomass production and fermentation rate, and their catabolites contribute to wine health benefits and sensorial character through the yeast biotransformation of grape juice constitutes into biologically active and flavor-impacting components. A UHPLC-MS/MS method was applied to monitor 37 tryptophan/phenylalanine/tyrosine yeast metabolites both in extra- and intracellular extracts produced by the fermentation of two Saccharomyces cerevisiae strains and one Torulaspora delbrueckii. The results shed light on the intra- and extra-cellular metabolomic dynamics, by combining metabolic needs, stimuli, and signals. Among others, the results indicated (a) the production of 2-aminoacetophenone by yeasts, mainly by the two Saccharomyces cerevisiae; (b) the deactivation and/or detoxification of tryptophol via sulfonation reaction; and (c) the deacetylation of N-acetyl tryptophan ethyl ester and N-acetyl tyrosine ethyl ester by producing the corresponding ethyl esters.

Efficiency of three intracellular extraction methods in the determination of metabolites related to tryptophan and tyrosine in winemaking yeast's metabolism by LC-HRMS.

Yeast nitrogen metabolism produces metabolites, whose origin in wines has scarcely been studied, with an important biological and organoleptic role. The present work focuses on comparing three intracellular extraction methods in order to elucidate efficiency of extraction while measuring the effect of temperature upon the integrity of the compounds related to the metabolism of tryptophan and tyrosine by yeast. Two UHPLC/HRMS methods to measure 16 metabolites were developed and validated. The validation provided optimum values of LOD (7.4·10-6 to 0.1 µg L-1), of LOQ (2·10-5 to 0.02 µg L-1) of precision (11-0.5% RSD) and repeatability (12-0.5% RSD). The removal of interfering molecules enabled matrix effects to be kept at low levels. The results pointed out that the low-temperature methods were more effective, providing better precision for 16 metabolites. The high-temperature extraction method may yield false enhanced compounds concentrations since they originate in cell wall macromolecules degradation.

Inhibition of VEGFR-2 Phosphorylation and Effects on Downstream Signaling Pathways in Cultivated Human Endothelial Cells by Stilbenes from Vitis Spp.

Stilbenes are phenolic compounds present in different higher plant families that have shown different biological activities, such as antioxidant properties and antitumoral and anti-atherosclerotic effects, among others. Angiogenesis is a key process involved in both cancer and cardiovascular diseases, the vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 being the main triggers. Certain polyphenol compounds, such as flavonoids, have shown a potent capacity to inhibit VEGF and, consequently, angiogenesis. The present work, therefore, aims to evaluate the potential effect of stilbenes on inhibiting VEGF and their subsequent effect on the downstream signaling pathway (PLCγ1, Akt, and eNOS). VEGFR-2 activation was studied through an ELISA assay in the HUVEC line, while the phosphorylation of intracellular downstream proteins PLCγ1, Akt, and eNOS was tested by Western blot. Student's t test was used to determine significant differences between samples. On the one hand, astringin, pallidol, and ω-viniferin showed the lowest IC50 values (2.90 ± 0.27, 4.42 ± 0.67, and 6.10 ± 1.29 µM, respectively) against VEGFR-2 activation. Additionally, VEGF-induced PLCγ1 phosphorylation was significantly inhibited by ε-viniferin, astringin, and ω-viniferin. However, ε-viniferin and pallidol simultaneously enhanced eNOS activation, proving to be via Akt activation in the case of ε-viniferin. For the first time, these data suggest that stilbenes such as astringin, pallidol, ω-viniferin, and ε-viniferin have a potential anti-angiogenic effect and they could be further considered as anti-VEGF ingredients in food and beverages. In addition, ε-viniferin and pallidol significantly allowed eNOS activation and could likely prevent the side effects caused by anti-VEGF hypertension drugs.

Risk assessment methodologies in the field of contaminants, food contact materials, technological ingredients and nutritional risks.

The programme aimed at training the fellow in the risk assessment guidelines proposed by the EFSA in the field of contaminants, food contact materials, technological ingredients and nutritional risks. It had a modular 'learning by doing' approach and a balanced learning/case studies and theory. Module 1 offered an insight into chemical risk assessment and conferred transferable skills for a proper application of the framework. The hands-on activities consisted of three case studies that went from a simple exercise on an official opinion, to working in a team with experts to produce a new opinion, to an individual work to obtain a publishable review manuscript. Module 2 was a training in experimental toxicology designed to create a toxicological basis and to enable the fellow to perform toxicological studies for risk assessment purposes. She joined the team working on cyanotoxins, gained experience with both EFSA and Organization of Economic Cooperation and Development (OECD) guidelines on genotoxicity and an insight into the developing of analytical methods suitable for risk assessment purposes. During module 3, the fellow was trained in nutritional risk assessment and involved in experimental work in chemical characterisation, biomarkers and mechanisms of action of bioactive compounds. This developed the critical perspective when assessing nutritional and health claims related the design of experiments, methods used, interpretation of results and human relevance. Module 4 provided a 'hand-on experience' in scientific risk communication as the fellow was encouraged and supported in the participation at local, national and international workshops and congresses presenting the outcomes of the three modules. Thus, the fellow was successfully integrated in the day-by-day workflow of the department, gaining first-hand practical experience in risk assessment in a multicultural and interdisciplinary context. This enabled a productive exchange of good practices and contributed to building a European risk assessment community.

Hydroxytyrosol Decreases LPS- and α-Synuclein-Induced Microglial Activation In Vitro.

Neuroinflammation is a common feature shared by neurodegenerative disorders, such as Parkinson's disease (PD), and seems to play a key role in their development and progression. Microglia cells, the principal orchestrators of neuroinflammation, can be polarized in different phenotypes, which means they are able to have anti-inflammatory, pro-inflammatory, or neurodegenerative effects. Increasing evidence supports that the traditional Mediterranean dietary pattern is related to the reduction of cognitive decline in neurodegenerative diseases. A considerable intake of plant foods, fish, and extra virgin olive oil (EVOO), as well as a moderate consumption of red wine, all characteristic of the Mediterranean diet (MD), are behind these effects. These foods are especially rich in polyphenols, being the most relevant in the MD hydroxytyrosol (HT) and their derivatives present in EVOO, which have demonstrated a wide array of biological activities. Here, we demonstrate that HT is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide and α-synuclein. We also study the possible molecular mechanisms involved in the anti-inflammatory effect of HT, including the study of nuclear factor kappa B (NF-кB), mitogen-activated protein kinases (MAPKs), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inflammasome. Our data support the use of HT to prevent the inflammation associated with PD and shed light into the relationship between MD and this neurological disorder.

Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating Microglia-Mediated Neuroinflammation.

Neuroinflammation is a pathological feature of quite a number of Central Nervous System diseases such as Alzheimer and Parkinson's disease among others. The hallmark of brain neuroinflammation is the activation of microglia, which are the immune resident cells in the brain and represents the first line of defense when injury or disease occur. Microglial activated cells can adopt different phenotypes to carry out its diverse functions. Thus, the shift into pro-inflammatory/neurotoxic or anti-inflammatory/neuroprotective phenotypes, depending of the brain environment, has totally changed the understanding of microglia in neurodegenerative disease. For this reason, novel therapeutic strategies which aim to modify the microglia polarization are being developed. Additionally, the understanding of how nutrition may influence the prevention and/or treatment of neurodegenerative diseases has grown greatly in recent years. The protective role of Mediterranean diet (MD) in preventing neurodegenerative diseases has been reported in a number of studies. The Mediterranean dietary pattern includes as distinctive features the moderate intake of red wine and extra virgin olive oil, both of them rich in polyphenolic compounds, such as resveratrol, oleuropein and hydroxytyrosol and their derivatives, which have demonstrated anti-inflammatory effects on microglia on in vitro studies. This review summarizes our understanding of the role of dietary phenolic compounds characteristic of the MD in mitigating microglia-mediated neuroinflammation, including explanation regarding their bioavailability, metabolism and blood-brain barrier.

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.