Hydroxytyrosol Supplementation Research Articles

Enhancing the stability of a red organic wine through hydroxytyrosol supplementation at bottling: A time-dependent analysis

The effect of the addition of hydroxytyrosol (HT) in a red organic wine (Sangiovese 85 % and Cabernet Sauvignon 15 %) was evaluated. After six months of storage in a concrete tank, the wines were spiked with HT in three different amounts (30, 60, 120 mg/750 mL in wine) and compared with a control bottled wine (no HT addition). The bottled wines were stored at room temperature and were opened after a period of one, three, six, nine and twelve months to perform chemical and sensory analyses (T1, T3, T6, T9, and T12, respectively). Storage time was the factor that most influenced all wines parameters with respect to the different treatments. However, wine added with 60 and 120 mg/750 mL HT had a lower amount of acetic acid than the control at T3 and T6. At T6, the measured HT was negatively correlated with acetic acid (R2 = 0.81), thus suggesting that HT preserved the wine from oxidation. Later, this trend was not confirmed. The content of HT spiked was stable over twelve months of bottle storage; only the endogenous HT, which is naturally present in wine, showed a decrease of 44 % after twelve months of bottle storage. Yellowness (b*) was higher in the 30 mg/750 mL at T9 compared to the other samples. Lightness (L*) showed a decrement of 11 %, while a* (redness) increased by 21 % from T1 to T12. After T6, the wine fortified with 120 mg/750 mL was preferred by the sensory panel; however, it was the only sample to be clustered by the panel at T9 and "red fruits," "spicy", and "astringency" sensory attributes played an important role in this separation.

Systemic Health Effects of Oleuropein and Hydroxytyrosol Supplementation: A Systematic Review of Randomized Controlled Trials.

Non-communicable diseases (NCDs) cause 41 million deaths annually, accounting for 74% of global fatalities. The so-called Mediterranean diet, with its especially significant consumption of olive oil, has shown promising results in reducing the risk of developing NCDs, such as cardiovascular, liver, or bone diseases. In the context of the nutritional health benefits of foods, phenolic compounds such as olive oil's main components, oleuropein (OLE) and hydroxytyrosol (HT), have been shown to possess different beneficial effects. However, no systematic review has evaluated the health-promoting effects of OLE and HT until now. Consequently, this systematic review analyzed 12 human randomized controlled trials (RCTs), involving 683 participants, to assess the effects of supplements, pure compounds, or enriched foods containing OLE and HT regarding systemic health outcomes, including CVD risk factors, liver parameters, and bone, joint, and cognitive health. The review found contrasting but encouraging results, with some studies reporting significant modulation of body weight, lipid profile, and glucose metabolism, and improvements in bone, joint, and cognitive functions. The studies described different dosages and forms of supplementation, ranging from 5 mg/d HT to 990 mL/d olive leaf infusion (320.8 mg OLE and 11.9 mg HT), highlighting the need for further research to determine the optimal dosing and duration. Despite the mixed outcomes, OLE and HT supplementation show potential for improving some of the cardiometabolic health outcomes and bone, joint, and cognitive health. However, further studies are necessary to understand their benefits better and address existing limitations.

The effect of Hydroxytyrosol on Spexin immunoreactivity in pancreatic islets and serum insulin levels in a Streptozotocin-induced experimental diabetes model in rats

Diabetes (DM), a major health problem worldwide, is associated with the loss of β cells in the pancreatic islets and decreased insulin secretion. Hydroxytyrosol (HxT) is a phenol found in high concentrations in olive oil. Spexin (SPX) plays a role in regulating many metabolisms such as glucose and energy. This study aimed to determine the effects of HxT on circulating insulin levels, histopathological changes in pancreatic islets, and SPX immunoreactivity in a Streptozotocin-induced experimental diabetes model (eDM) in rats. The 32 male rats used in the study were randomly divided into 4 groups (n: 8): Control, eDM, eDM+HxT, and HxT. After completing all applications in the experiment, the blood and pancreas tissues of the sacrificed rats were taken. Insulin levels were determined from the serum samples obtained. Histopathological changes and SPX immunoreactivities were evaluated in pancreatic tissues. While serum insulin levels decreased in eDM, histopathological changes in pancreatic islets increased. Additionally, SPX immunoreactivity in pancreatic islets was significantly reduced in eDM. On the other hand, HxT supplementation (eDM+HxT group) regulated eDM-related adverse effects. While HxT supplementation may have a curative and therapeutic effect in DM, it was concluded that SPX may be effective in regulating the endocrine functions of the pancreas.

Long-Term Effect of Maternal Antioxidant Supplementation on the Lipid Profile of the Progeny According to the Sow's Parity Number.

Pig feeding prior to the extensive fattening phase might affect the final lipid profile and product quality. This study evaluates how maternal supplementation with vitamin E (VITE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg), or combined administration (VE + HXT) affects the piglet's plasma and tissues' fatty acid profiles and lipid stability according to the sow's parity number (PN), as well as the possible changes to the lipid profile after extensive feeding. The sows' PN affected the total fatty acid profile of plasma, muscle, and liver of piglets, with lower Δ-9 and Δ-6 desaturase indices but higher Δ-5 in those from primiparous (P) than multiparous (M) sows. Dietary VITE was more effective at decreasing C16:0 and saturated fatty acids in the muscle of piglets born from M than P sows, and modified the liver phospholipids in a different way. Sows' supplementation with HXT increased C18:2n-6 in triglycerides and polyunsaturated fatty acids (PUFA) in muscle phospholipids. In the liver, HXT supplementation also increased free-PUFA and free-n-3 fatty acids. However, lipid oxidation of piglets' tissues was not affected by the antioxidant supplementation, and it was higher in the livers of piglets born from M sows. The fatty acid profile in the muscle of pigs after extensive feeding was not affected by the PN, but it was by the sows' antioxidant supplementation, with positive effects on quality by both compounds.

Dietary Hydroxytyrosol Supplementation on Growth Performance, Gut Morphometry, and Oxidative and Inflammatory Status in LPS-Challenged Broilers.

This study assessed the effects of hydroxytyrosol (HT) on 8- to 20-day-old broilers challenged with lipopolysaccharide (LPS); 180 Cobb500™ male chicks were randomly assigned to 3 treatment groups, each comprising 10 replicates with 6 birds per replicate. Treatments included a control diet (CON), CON with LPS administration, and CON + LPS supplemented with 10 mg of HT/kg of feed. LPS was administered intraperitoneally on days 14, 16, 18, and 20. Body weight (BW), body weight gain (BWG), and the feed conversion ratio (FCR) were measured. On day 20, ten birds per treatment were slaughtered for analysis. Bursa, spleen, and liver were collected, and their respective relative weight was determined. The jejunum was destined for morphological analyses of villus height (VH), crypt depth (CD), and their ratio (VH:CD), and for mRNA expression of nuclear factor kappa B (NF-κB), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), and interleukins 10 (IL-10), 1 beta (IL-1β), and 8 (IL-8). HT improved BW, BWG, and FCR, and reduced crypt depth (CD) while increasing the VH:CD ratio in the jejunum. Moreover, HT downregulated mRNA expression of CAT, GPx, IL-10, and IL-1β. In conclusion, HT enhances broiler growth performance, mitigates jejunal mucosa damage from LPS, and modulates antioxidant and immune responses.

Effects of quercetin and hydroxytyrosol supplementation in a high-fat diet on growth, lipid metabolism, and mitochondrial function in spotted seabass (Lateolabrax maculatus)

Endoplasmic reticulum (ER) stress and mitochondrial impairment commonly occur during the progression of fatty liver disease. There is a close connection and crosstalk between mitochondria and ER. The potential positive influence of mitigating ER stress (ERS) and mitochondrial damage in the context of preventing and treating fatty liver was explored in spotted seabass (Lateolabrax maculatus) as a susceptible model to fatty liver. A normal-fat diet (11% fat, NFD) and a high-fat diet (17% fat, HFD) were formulated and three additional diets were prepared by supplementation of quercetin (QUE) (0.1%), hydroxytyrosol (HT) (0.02%) or their combination (0.1% QUE + 0.02% HT) to the HFD (HFD + QUE HFD + HT and HFD + QUE + HT diets).Three replicate groups of fish (25 ± 0.02 g) were fed the test diets to visual satiety for 8 weeks. The results revealed the deterioration of growth, feed intake and feed utilization in HFD group compared to the NFD group whereas QUE and HT application improved their values and the optimum results were achieved for the HFD + QUE + HT group. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and both serum and hepatic triglyceride (TG), total cholesterol (T-CHO) and non-esterified free fatty acids (NEFA) concentrations were enhanced in HFD group, and their values decreased by QUE and HT, particularly their combined supplementation. The results of oil red O staining exhibited a remarkable reduction in number of lipid droplets in the liver of fish from HFD + QUE + HT group compared to the HFD group. Whole-body and muscle fat contents and abdominal fat index decreased by QUE and HT application. Expression of lipid metabolism related genes (srebp-1c, fas, acc) were down-regulated by QUE and HT treatment. Co-supplementation of QUE and HT down-regulated the expression of ERS-related genes (grp78, chop, perk, atf6, ire1), improved ER ultrastructure, and enhanced the coupling between mitochondria and ER. Moreover, expression of genes associated with hepatic mitochondrial biogenesis (pgc1-α, pgc1-β, nrf1) and mitophagy (pink1, atg5, mul1) was up-regulated in HFD + QUE, HFD + HT and HFD + QUE + HT groups. These data suggest that combined supplementation of QUE and HT in HFD for spotted seabass can improve growth and feed utilization, reduce hepatic damage and fat accumulation, and alleviate HFD induced ERS and mitochondrial dysfunction.

Effects of Hydroxytyrosol Supplementation on Performance, Fat and Blood Parameters of Broiler Chickens.

The study aimed to evaluate the effects of dietary supplementation of hydroxytyrosol (HT) on performance, fat, and blood parameters of broilers. In total, 960 male chicks were distributed into four treatments groups with 12 replicates with 20 birds per pen, with varying HT levels (0, 5, 10, and 50 mg/kg of feed) added to the basal diet from 1 to 42 days old. Feed intake, body weight gain, and feed conversion ratio were evaluated. Enzymes related to liver injury were evaluated in blood. Fatty acid profile and malondialdehyde (MDA) concentration were determined in the breast meat. Dietary supplementation of HT did not improve broilers' performance (p > 0.05). Birds fed 50 mg HT/kg had lower AST, ALT, and GGT concentrations (p ≤ 0.05), whereas broilers fed 5, 10, and 50 mg HT/kg, had lower TBIL concentrations (p ≤ 0.05). Breast meat of broilers fed 50 mg HT/kg had lower lipid content, saturated fatty acid, unsaturated fatty acids, MDA concentrations (p ≤ 0.05), and polyunsaturated fatty acids (p < 0.0001). In summary, supplementation of 5, 10, and 50 mg HT/kg does not improve the performance of broilers, but the dose of 50 mg HT/kg helps the liver against inflammation and improves fat parameters.

Hydroxytyrosol Induces Dyslipidemia in an ApoB100 Humanized Mouse Model.

Extra virgin olive oil has numerous cardiopreventive effects, largely due to its high content of (poly)phenols such as hydroxytyrosol (HT). However, some animal studies suggest that its excessive consumption may alter systemic lipoprotein metabolism. Because human lipoprotein metabolism differs from that of rodents, this study examines the effects of HT in a humanized mouse model that approximates human lipoprotein metabolism. Mice are treated as follows: control diet or diet enriched with HT. Serum lipids and lipoproteins are determined after 4 and 8 weeks. We also analyzed the regulation of various genes and miRNA by HT, using microarrays and bioinformatic analysis. An increase in body weight is found after supplementation with HT, although food intake was similar in both groups. In addition, HT induced the accumulation of triacylglycerols but not cholesterol in different tissues. Systemic dyslipidemia after HT supplementation and impaired glucose metabolism are observed. Finally, HT modulates the expression of genes related to lipid metabolism, such as Pltp or Lpl. HT supplementation induces systemic dyslipidemia and impaired glucose metabolism in humanized mice. Although the numerous health-promoting effects of HT far outweigh these potential adverse effects, further carefully conducted studies are needed.

Hydroxytyrosol produced by engineered Escherichia coli strains activates Nrf2/HO-1 pathway: An in vitro and in vivo study.

This study explores the biological effects of hydroxytyrosol (HT), produced by the metabolic engineering of Escherichia coli, in a series of in vitro and in vivo experiments. In particular, a metabolically engineered Escherichia coli strain capable of producing HT was constructed and utilized. HEK293 and HeLa cells were exposed to purified HT to determine non-toxic doses that can offer protection against oxidative stress (activation of Nrf2/HO-1 signaling pathway). Male CD-1 mice were orally supplemented with HT to evaluate (1) renal and hepatic toxicity, (2) endogenous system antioxidant response, and (3) activation of Nrf2/HO-1 system in the liver. HT protected cells from oxidative stress through the activation of Nrf2 regulatory network. Activation of Nrf2 signaling pathway was also observed in the hepatic tissue of the mice. HT supplementation was safe and produced differential effects on mice's endogenous antioxidant defense system. HT biosynthesized from genetically modified Escherichia coli strains is an alternative method to produce high-quality HT that exerts favorable effects in the regulation of the organism's response to oxidative stress. Nonetheless, further investigation of the multifactorial action of HT on the antioxidant network regulation is needed.

Different Effect of Vitamin E or Hydroxytyrosol Supplementation to Sow's Diet on Oxidative Status and Performances of Weaned Piglets.

Different feeding strategies are being applied to sows in order to obtain homogeneous piglets' weights and improved health status. This study evaluated how the dietary supplementation of vitamin E (VE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg) or the combined administration (VE + HXT) given to Iberian sows from day 85 of gestation affected the growth pattern of the piglets and their oxidative status; and quantified what these effects were due to. Dietary VE and HXT improved the oxidative status of sows and piglets. Both VE and HXT modified the growth pattern at birth and performances of the piglets in a different way according to the growing period. Piglets' performances were positively correlated with plasma VE and negatively with plasma malondialdehyde (MDA) of the sow. However, the highest variation in growth patterns was explained by the colostrum composition. Significant linear equations were observed between piglets' performances and colostrum saturated (SAT), n-7 monounsaturated fatty acids (C16:1n-7 and C18:1n-7) and different desaturases indices. This study would confirm that VE supplementation to the sow diet could be more adequate than HXT for the improved development during the first weeks of a piglet's life. The combined administration of both antioxidants would not produce additional positive effects compared to the individual supplementation.

Dietary Vitamin E and/or Hydroxytyrosol Supplementation to Sows during Late Pregnancy and Lactation Modifies the Lipid Composition of Colostrum and Milk.

Modifying the composition of a sow's milk could be a strategy to improve the intestinal health and growth of her piglet during the first weeks of life. This study evaluated how dietary supplementation of vitamin E (VE), hydroxytyrosol (HXT) or VE+HXT given to Iberian sows from late gestation affected the colostrum and milk composition, lipid stability and their relationship with the piglet's oxidative status. Colostrum from VE-supplemented sows had greater C18:1n-7 than non-supplemented sows, whereas HXT increased polyunsaturated (∑PUFAs), ∑n-6 and ∑n-3 fatty acids. In 7-day milk, the main effects were induced by VE supplementation that decreased ∑PUFAs, ∑n-6 and ∑n-3 and increased the Δ-6-desaturase activity. The VE+HXT supplementation resulted in lower desaturase capacity in 20-day milk. Positive correlations were observed between the estimated mean milk energy output and the desaturation capacity of sows. The lowest concentration of malondialdehyde (MDA) in milk was observed in VE-supplemented groups, whereas HXT supplementation increased oxidation. Milk lipid oxidation was negatively correlated with the sow's plasma oxidative status and to a great extent with the oxidative status of piglets after weaning. Maternal VE supplementation produced a more beneficial milk composition to improve the oxidative status of piglets, which could promote gut health and piglet growth during the first weeks, but more research is needed to clarify this.

Efficacy of Hydroxytyrosol-Rich Food Supplements on Reducing Lipid Oxidation in Humans.

In the present study we report the efficacy of two food supplements derived from olives in reducing lipid oxidation. To this end, 12 healthy volunteers received a single dose (25 mL) of olive phenolics, mainly hydroxytyrosol (HT), provided as a liquid dietary supplement (30.6 or 61.5 mg HT), followed by an investigation of two reliable markers of oxidative stress. Blood and urine samples were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 12 h post-intake. Plasma-oxidized low-density lipoprotein (oxLDL) cholesterol levels were measured with ELISA using a monoclonal antibody, while F2-isoprostanes (F2-IsoPs) were quantified in urine with UHPLC-DAD-MS/MS. Despite the great variability observed between individuals, a tendency to reduce lipoxidation reactions was observed in the blood in response to a single intake of the food supplements. In addition, the subgroup of individuals with the highest baseline oxLDL level showed a significant (p < 0.05) decrease in F2-IsoPs at 0.5 and 12 h post-intervention. These promising results suggest that HT supplementation could be a useful aid in preventing lipoxidation. Additionally, people with a redox imbalance could benefit even more from supplementing with bioavailable HT.

Approaches in Hydroxytyrosol Supplementation on Epithelial-Mesenchymal Transition in TGFβ1-Induced Human Respiratory Epithelial Cells.

Hydroxytyrosol (HT) is an olive polyphenol with anti-inflammatory and antioxidant properties. This study aimed to investigate the effect of HT treatment on epithelial-mesenchymal transition (EMT) in primary human respiratory epithelial cells (RECs) isolated from human nasal turbinate. HT dose-response study and growth kinetic study on RECs was performed. Several approaches on HT treatment and TGFβ1 induction with varying durations and methods was studied. RECs morphology and migration ability were evaluated. Vimentin and E-cadherin immunofluorescence staining and Western blotting [E-cadherin, vimentin, SNAIL/SLUG, AKT, phosphorylated (p)AKT, SMAD2/3 and pSMAD2/3] were performed after 72-h treatment. In silico analysis (molecular docking) of HT was performed to evaluate the potential of HT to bind with the TGFβ receptor. The viability of the HT-treated RECs was concentration-dependent, where the median effective concentration (EC50) was 19.04 μg/mL. Testing of the effects of 1 and 10 µg/mL HT revealed that HT suppressed expression of the protein markers vimentin and SNAIL/SLUG while preserving E-cadherin protein expression. Supplementation with HT protected against SMAD and AKT pathway activation in the TGFβ1-induced RECs. Furthermore, HT demonstrated the potential to bind with ALK5 (a TGFβ receptor component) in comparison to oleuropein. TGFβ1-induced EMT in RECs and HT exerted a positive effect in modulating the effects of EMT.

O130 Dietary vitamin E and/or hydroxytyrosol supplementation to sows during late pregnancy and lactation improves early post-natal development of the offspring

O130 Dietary vitamin E and/or hydroxytyrosol supplementation to sows during late pregnancy and lactation improves early post-natal development of the offspring

Comment on Yeste et al. Polyphenols and IUGR Pregnancies: Intrauterine Growth Restriction and Hydroxytyrosol Affect the Development and Neurotransmitter Profile of the Hippocampus in a Pig Model. Antioxidants 2021, 10, 1505.

Intrauterine growth restriction (IUGR) affects 5–10% of newborns and increases the risks of intrauterine demise, neonatal morbidity, and death. In their recent publication, Yeste et al. found the benefits of hydroxytyrosol supplementation on brain remodeling from an IUGR pig model. Additionally, we found a significant decrease in phenolic alcohol (tyrosol and hydroxytyrosol) intake in IUGR pregnant women. Altogether, these findings support the notion that dietetic interventions, through supplementation but mostly via a balanced diet, can ameliorate IUGR complications. Furthermore, diet intervention combined with early biomarkers may allow clinicians to eventually anticipate IUGR diagnosis and help avoid one of the most frequent causes of newborn mortality and morbidity.

Hydroxytyrosol alleviates dextran sodium sulfate–induced colitis by inhibiting NLRP3 inflammasome activation and modulating gut microbiota in vivo

ObjectiveAn increase in the global prevalence of inflammatory bowel disease has been reported in recent years. Although its pathogenesis has not been fully elucidated, inflammatory bowel disease is highly correlated with intestinal oxidative stress, immune disorders, overexpression of proinflammatory factors, and imbalance of gut microbiota. Hydroxytyrosol (HT), extracted from olive oil and leaves, exhibits significant antioxidant and antiinflammatory activities. MethodsTherefore, this study sought to evaluate whether the antiinflammatory effect of HT on dextran sodium sulfate (DSS)–induced ulcerative colitis in mice is regulated by targeting the NLRP3 inflammasome and gut microbiota. ResultsColon pathologic morphology and apoptosis were found to be ameliorated in the DSS + HT group compared to the DSS group. Antioxidant capacity was higher in the DSS + HT group than in the DSS group (P < 0.01). HT suppressed expression levels of NLRP3, caspase-1, and ASC mRNA and downregulated interleukin-18 and interleukin-1β levels in the DSS group (P < 0.01). Furthermore, HT exerted a shift from pathogens to probiotics, and increased the levels of short-chain fatty acids (P < 0.01) in the DSS group. ConclusionIn summary, HT supplementation exerts antiinflammatory effects in DSS-induced ulcerative colitis by enhancing colonic antioxidant capacities, inhibiting NLRP3 inflammasome activation, and modulating gut microbiota in vivo.

Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet.

Objective: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. Methods: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). Results: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. Conclusion: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.

Hydroxytyrosol ameliorates oxidative challenge and inflammatory response associated with lipopolysaccharide-mediated sepsis in mice.

Hydroxytyrosol (HT) is among the main bioactive ingredients isolated from olive tree with a variety of biological and pharmacological activities. In the current study, the antioxidative and anti-inflammatory activities of HT were distinguished in the splenic tissue following lipopolysaccharide (LPS)-mediated septic response. Thirty-five Swiss mice were divided into five groups (n = 7): control, HT (40 mg/kg), LPS (10 mg/kg), HT 20 mg+LPS and HT 40 mg+LPS. HT was administered for 10 days, while a single LPS dose was applied. The obtained findings demonstrate that HT administration enhanced the survival rate and decreased lactate dehydrogenase level in LPS-challenged mice. Treatment with HT inhibited the incidence of oxidative damage in splenic tissue through decreasing lipoperoxidation and increasing antioxidant molecules, namely glutathione, superoxide dismutase and catalase. HT also decreased total leukocytes count, C-reactive protein, monocyte chemoattractant protein-1, and myeloperoxidase levels. Additionally, HT suppressed the production levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6. Moreover, mRNA expression of inducible nitric oxide synthase and nitric oxide production were increased after HT administration. Furthermore, HT supplementation resulted in a downregulation of p38 mitogen-activated protein kinase, inhibited the activation of the nuclear factor kappa-B from the nucleus to the cytoplasm, and attenuated infiltration of activated immune cells and tissue injury following LPS injection. Collectively, these findings demonstrate the antioxidative and anti-inflammatory properties of HT against LPS-mediated inflammation and sepsis. Therefore, HT could be applied as an alternative anti-inflammatory agent to minimize or prevent the development of systemic inflammatory response associated with septic shock.

Hydroxytyrosol Attenuates Hepatic Fat Accumulation via Activating Mitochondrial Biogenesis and Autophagy through the AMPK Pathway.

Two experiments were carried out to examine the impacts of hydroxytyrosol (HT) on lipid metabolism and mitochondrial function in Megalobrama amblycephala. Triplicate groups of fish were fed four test diets: (1) low-fat diet (LFD, 5% fat), (2) high-fat diet (HFD, 15% fat), (3) LFD + 100 mg/kg HT (LFD + HT), and (4) HFD + 100 mg/kg HT (HFD + HT) (in vivo). Hepatocytes from the same batch were exposed to three media including L-15 medium (L15), oleic acid (OA) medium [L15 + 400 μM OA], and OA + HT medium [L15 + 400 μM OA + 10 μM HT] to explore the roles of HT in mitochondrial function (in vitro). Fish fed HFD had excessive fat deposition in the liver, and HT inclusion in the HFD decreased hepatic fat deposition. Transmission electron microscopy revealed that the HFD triggers loss of cristae and metrical density and hydropic changes in mitochondria and that HT supplementation attenuates the ultrastructural alterations of mitochondria. The in vitro test showed that HT decreases fat deposition in hepatocytes, suppresses the reactive oxygen species formation, and facilitates the expression of phospho-AMPK protein and the genes involved in mitochondria biogenesis (PGC-1, NRF-1, TFAM) and autophagy (PINK1, Mul1, Atg5). These findings suggest the lipid-lowering effect of HT mediated by activation of mitochondrial biogenesis and autophagy through the AMPK pathway.

Delivery Systems for Hydroxytyrosol Supplementation: State of the Art

This review aims to highlight the benefits and limitations of the main colloid-based available delivery systems for hydroxytyrosol. Hydroxytyrosol is a phenolic compound with clear biological activities for human wellness. Olive fruits, leaves and extra-virgin oil are the main food sources of hydroxytyrosol. Moreover, olive oil mill wastewaters are considered a potential source to obtain hydroxytyrosol to use in the food industry. However, recovered hydroxytyrosol needs adequate formulations and delivery systems to increase its chemical stability and bioavailability. Therefore, the application of hydroxytyrosol delivery systems in food sector is still a fascinating challenge. Principal delivery systems are based on the use of colloids, polymers able to perform gelling, thickening and stabilizing functions in various industrial sectors, including food manufacturing. Here, we review the recipes for the available hydroxytyrosol systems and their relative production methods, as well as aspects relative to system characteristics and hydroxytyrosol effectiveness.