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1.
J Agric Food Chem ; 68(5): 1248-1256, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31927921

RESUMO

Lipophenols are regarded as an emerging source of functional food ingredients. However, little is known about their in vivo digestion, absorption, and metabolism. Thus, the pharmacokinetic characteristics in rat and the gut microbial degradation of tyrosol acyl esters (TYr-Es) with fatty acids of C12:0, C18:0, and C18:2 were investigated for the first time. Major metabolites including tyrosol sulfate and tyrosol glucuronide, rather than the parent compounds, were detected in rat plasma after oral administration of TYr-Es. The increased plasma half-life (T1/2) and mean residence time demonstrated that TYr-Es display a longer duration of action in vivo than TYr, potentially leading to higher oral bioavailability. TYr-Es could be hydrolyzed by the gut microbiota to free TYr, which may result in the appearance of the second absorption peak in pharmacokinetic profiles. Therefore, TYr-Es exhibit improved bioavailability compared to that of TYr because of their prolonged duration of action.


Assuntos
Ésteres/farmacocinética , Álcool Feniletílico/análogos & derivados , Animais , Disponibilidade Biológica , Ésteres/química , Ácidos Graxos/sangue , Ácidos Graxos/química , Cinética , Masculino , Álcool Feniletílico/química , Álcool Feniletílico/farmacocinética , Plasma/química , Ratos , Ratos Sprague-Dawley
2.
Appl Biochem Biotechnol ; 190(1): 148-165, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31313241

RESUMO

Feasibility and stability were evaluated of a continuous multi-batch process for converting oleuropein (OLE) from olive leaf extract to the bioactive product hydroxytyrosol (HT). Carrier beads made of three different materials (calcium alginate, chitosan with deacetylated α-chitin nanofibers (DEChN), or porous ceramic) were investigated for morphology, thermogravimetric, sorption, and viscoelastic properties. Enzymatic hydrolysis of OLE conducted in a packed bed bioreactor containing cellulase immobilized to carrier beads yielded OLE degradation rates of ~ 90% and an average HT yield of ~ 70% over 20 batches. Ultimately, inorganic porous ceramic beads were less costly and exhibited superior performance relative to organic carriers and thus were deemed most suitable for industrial-scale HT production. Systems utilizing enzyme immobilization within packed bed reactors hold promise for achieving efficient production of valuable bioproducts from discarded biomass materials.


Assuntos
Celulase/metabolismo , Enzimas Imobilizadas/metabolismo , Iridoides/metabolismo , Olea/metabolismo , Álcool Feniletílico/análogos & derivados , Folhas de Planta/metabolismo , Alginatos/química , Biomassa , Reatores Biológicos , Cerâmica , Quitosana/química , Hidrólise , Microscopia Eletrônica de Varredura , Álcool Feniletílico/metabolismo , Especificidade por Substrato , Termogravimetria
3.
Food Chem ; 308: 125646, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31654977

RESUMO

Hydroxytyrosol (HT), which is a polyphenol with a high antioxidant power and many associated health benefits, has been found in wines. Wine yeasts are capable of producing high amounts of the higher alcohol tyrosol, which is the precursor for HT synthesis. We have improved the ability of Saccharomyces cerevisiae to produce HT by heterologously expressing the HpaBC enzyme complex of Escherichia coli, which hydroxylates tyrosol into HT. By overexpressing the hpaB and hpaC genes, we achieved HT titers of 1.15 ±â€¯0.05 mg/L and 4.6 ±â€¯0.9 mg/L in a minimal medium in which either 1 mM tyrosine or 1 mM tyrosol were respectively added. This work demonstrates that the overexpression of HpaBC in yeast is a promising tool to overproduce HT at the expense of endogenous tyrosol through central carbon catabolism flux redirection to tyrosine catabolism.


Assuntos
Escherichia coli/metabolismo , Oxigenases de Função Mista/metabolismo , Álcool Feniletílico/análogos & derivados , Saccharomyces cerevisiae/metabolismo , Escherichia coli/genética , Oxigenases de Função Mista/genética , Álcool Feniletílico/metabolismo , Saccharomyces cerevisiae/genética
4.
Cell Physiol Biochem ; 53(6): 921-932, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778305

RESUMO

BACKGROUND/AIMS: Lysophosphatidic acid (LPA) is a phospholipid signal molecule that regulates many cellular processes both physiological and pathological. Moreover, its high plasma concentrations are toxic for several cellular types, including erythrocytes (RBC), as it acts as a pro-thrombotic and pro-atherogenic agent. It is therefore essential to explore the potential protective role of nutrition in protecting cells from the possible toxic effects of high plasma concentrations of LPA by testing bioactive nutrients. In particular, our focus was on hydroxytyrosol (HT), a phenolic antioxidant occurring naturally in virgin olive oil, investigating its possible protective effect in preventing LPA-induced programmed cell death (eryptosis) in human RBC. METHODS: Intact RBC were incubated in the presence of 2.5 µM LPA and increasing concentrations of HT. Phosphatidylserine (PS) exposure with cell shrinkage, influx of extracellular calcium (Ca2+), adenosine triphosphate (ATP) and glutathione levels were measured by FACS analysis. In addition, confocal laser scanning microscopy was used to determine RBC morphological alterations, as well as microvesicle formation. RESULTS: Our study confirms that LPA-induced eryptosis is characterized by PS exposure at the cell surface, with cell shrinkage and ATP and glutathione depletion; (Ca2+) influx is also a key event that triggers eryptosis. Here we report for the first time that cell co-incubation with LPA and in quantities as low as 0.1 µM HT causes a significant decrease in PS-exposing RBC, in addition to providing significant protection from the decrease in cell volume. Moreover, treatment of RBC with HT counters the influx of extracellular Ca2+ and completely restores ATP and glutathione content at 1 µM. Finally, under the same experimental conditions, HT exerts a protective effect on RBC morphological changes and microvescicle release, completely restoring the typical biconcave shape at 1 µM. CONCLUSION: Taken together, the findings reported in this paper point to a novel biological effect for HT in preventing programmed suicidal death in anucleated cells and indicate that prevention from LPA toxic effects may represent an additional mechanism responsible for the health-promoting effect of this dietary phenol which has been claimed, particularly related to cardiovascular diseases.


Assuntos
Eriptose/efeitos dos fármacos , Lisofosfolipídeos/toxicidade , Álcool Feniletílico/análogos & derivados , Fosfatidilserinas/farmacologia , Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Tamanho Celular/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa/metabolismo , Humanos , Álcool Feniletílico/farmacologia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
5.
J Cardiovasc Med (Hagerstown) ; 20(7): 419-426, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31593559

RESUMO

BACKGROUND AND AIM: Cardiovascular diseases (CVDs) are the most frequent causes of death in the world. Inflammation and oxidative damage contribute significantly to the development of atherosclerosis and CVDs. European Food Safety Authority scientific opinion has acknowledged that hydroxytyrosol (3,4-dihydroxyphenylethanol) and derivatives, contained in extra virgin olive oil (EVOO), typically used in Mediterranean diet may play a crucial role in the reduction of the inflammatory pathway and in the prevention of CVDs. The aim of the study was to determine the effect in healthy volunteers of 25 g of phenols-rich EVOO (p-EVOO). METHODS: The clinical study was a randomized, controlled trial to determine the acute effect in the postprandial time of 25 g of p-EVOO. We evaluated nutritional status using anthropometric parameters, body composition, serum metabolites, oxidative stress biomarkers and gene expression of eight genes related to oxidative stress and human inflammasome pathways, lasting 2 h after p-EVOO administration. Twenty-two participants resulted as eligible for the study. RESULTS: A significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index was highlighted (P < 0.05). Significant upregulation of catalase, superoxide dismutase 1 and upstream transcription factor 1 were observed (P < 0.05). CONCLUSION: The current study shows that intake of 25 g of p-EVOO has been able to be modulated, in the postprandial time, the antioxidant profile and the expression of inflammation and oxidative stress-related genes, as superoxide dismutase 1, upstream transcription factor 1 and catalase. We also observed a significant reduction of oxidized LDL, malondialdehyde, triglycerides and visceral adiposity index. We have demonstrated that a daily intake of phenols and antioxidants can reduce the inflammatory pathway and oxidative stress and therefore the risk of atherosclerosis and CVDs. More studies on a larger population are necessary before definitive conclusions can be drawn.Trial registration ClinicalTrials.gov NCT01890070.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Lipoproteínas LDL/sangue , Nutrigenômica/métodos , Azeite de Oliva/metabolismo , Estresse Oxidativo/genética , Fenóis/sangue , Álcool Feniletílico/análogos & derivados , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , Catalase/sangue , Catalase/genética , Dieta Mediterrânea , Método Duplo-Cego , Feminino , Humanos , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Azeite de Oliva/administração & dosagem , Álcool Feniletílico/sangue , Período Pós-Prandial , Fatores de Proteção , Fatores de Risco , Roma , Superóxido Dismutase-1/sangue , Superóxido Dismutase-1/genética , Fatores Estimuladores Upstream/sangue , Fatores Estimuladores Upstream/genética , Adulto Jovem
6.
Food Funct ; 10(9): 6170-6183, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501836

RESUMO

High-fat-diet (HFD) feeding is associated with liver oxidative stress (OS), n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) depletion, hepatic steatosis and mitochondrial dysfunction. Our hypothesis is that the HFD-induced liver injury can be attenuated by the combined supplementation of n-3 LCPUFA eicosapentaenoic acid (EPA) and the antioxidant hydroxytyrosol (HT). The C57BL/6J mice were administered an HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg kg-1 day-1), HT (5 mg kg-1 day-1), or EPA + HT (50 and 5 mg kg-1 day-1, respectively) for 12 weeks. We measured the body and liver weights and dietary and energy intakes along with liver histology, FA composition, steatosis score and associated transcription factors, mitochondrial functions and metabolic factors related to energy sensing through the AMP-activated protein kinase (AMPK) and PPAR-γ coactivator-1α (PGC-1α) cascade. It was found that the HFD significantly induced liver steatosis, with a 66% depletion of n-3 LCPUFAs and a 100% increase in n-6/n-3 LCPUFA ratio as compared to the case of CD (p < 0.05). These changes were concomitant with (i) a 95% higher lipogenic and 70% lower FA oxidation signaling, (ii) a 40% diminution in mitochondrial respiratory capacity and (iii) a 56% lower ATP content. HFD-induced liver steatosis was also associated with (iv) a depressed mRNA expression of AMPK-PGC-1α signaling components, nuclear respiratory factor-2 (NRF-2) and ß-ATP synthase. These HFD effects were significantly attenuated by the combined EPA + HT supplementation in an additive manner. These results suggested that EPA and HT co-administration partly prevented HFD-induced liver steatosis, thus strengthening the importance of combined interventions in hepatoprotection in non-alcoholic fatty liver disease.


Assuntos
Ácido Eicosapentaenoico/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Álcool Feniletílico/análogos & derivados , Trifosfato de Adenosina/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais/análise , Sinergismo Farmacológico , Ácidos Graxos Ômega-3/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/genética , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Humanos , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Álcool Feniletílico/administração & dosagem
7.
Food Chem Toxicol ; 134: 110817, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31521636

RESUMO

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.


Assuntos
Hidroxibenzoatos/farmacologia , Melatonina/farmacologia , Fármacos Neuroprotetores/farmacologia , Álcool Feniletílico/análogos & derivados , alfa-Sinucleína/toxicidade , Animais , Proteínas de Choque Térmico HSP70/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Células PC12 , Álcool Feniletílico/farmacologia , Ratos , Sirtuína 2/metabolismo
8.
Nutrients ; 11(9)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546768

RESUMO

Collecting dietary intake data is associated with challenges due to the subjective nature of self-administered instruments. Biomarkers may objectively estimate the consumption of specific dietary items or help assess compliance in dietary intervention studies. Our aim was to use a panel of plasma and urine biomarkers to assess the validity of self-reported dietary intake using a modified Mediterranean Diet Scale (mMDS) among firefighters participating in Feeding America's Bravest (FAB), an MD cluster-randomized controlled trial. In our nested biomarker pilot study, participants were randomly selected from both the MD intervention group (n = 24) and the control group (n = 24) after 12-months of dietary intervention. At baseline data collection for the pilot study (t = 12-months of FAB), participants in the control group crossed-over to receive the MD intervention (active intervention) for 6-months. Participants in the intervention group continued in a self-sustained continuation phase (SSP) of the intervention. Food frequency questionnaires (FFQ), 13-item-mMDS questionnaires, 40 plasma fatty acids, inflammatory biomarkers and urinary hydroxytyrosol and tyrosol were analyzed at both time points. Spearman's correlation, t-tests and linear regression coefficients were calculated using SAS software. Overall, the mMDS derived from the FFQ was highly correlated with the specific 13-domain-mMDS (r = 0.74). The concordance between the two questionnaires for low and high adherence to MD was high for all the participants in the parent trial (κ = 0.76). After 6 months of intervention in the pilot study, plasma saturated fatty acid decreased in both groups (active intervention: -1.3 ± 1.7; p = 0.002; SSP: -1.12 ± 1.90; p = 0.014) and oleic acid improved in the SSP (p = 0.013). Intake of olive oil was positively associated with plasma omega-3 (p = 0.004) and negatively with TNF-α (p < 0.001) at baseline. Choosing olive oil as a type of fat was also associated with higher levels of plasma omega-3 (p = 0.019) at baseline and lower TNF-α (p = 0.023) at follow up. Intake of red and processed meats were associated with lower serum omega-3 (p = 0.04) and fish consumption was associated with lower IL-6 at baseline (p = 0.022). The overall mMDS was associated with an increase in plasma omega-3 (p = 0.021). Good correlation was found between nutrient intake from the FFQ and the corresponding plasma biomarkers (omega-3, EPA and DHA). In this MD randomized controlled trial, some key plasma biomarkers were significantly associated with key MD diet components and the overall mMDS supporting the validity of the mMDS questionnaire as well as compliance with the intervention.


Assuntos
Dieta Mediterrânea , Bombeiros , Biomarcadores/sangue , Biomarcadores/urina , Estudos Cross-Over , Ácidos Graxos/sangue , Humanos , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/urina , Projetos Piloto , Reprodutibilidade dos Testes , Inquéritos e Questionários , Estados Unidos
9.
Nutrients ; 11(9)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31500145

RESUMO

The objective of this study was to determine the acute (one single dose), subacute (14 days), and sub-chronic (90 days) toxicity of an aqueous virgin olive oil (VOO) extract rich in hydroxytyrosol in rats. For acute/subacute toxicity, rats were divided into three groups. The control group received distilled water (n = 9), another experimental group received a single dose of 300 mg/kg (n = 3), and a third group received one dose of 2000 mg/kg (n = 4) during 14 days. The sub-chronic study included 60rats distributed in three groups (n = 20: 10 males and 10 females) receiving daily different three doses of the VOO extract in the drinking water during 90 days: (1) 100 mg/kg, (2) 300 mg/kg, and (3) 1000 mg/kg. In parallel, a fourth additional group (n = 20: 10 males and 10 females) did not receive any extract (control group). Clinical signs, body weight, functional observations of sensory and motor reactivity, hematological and biochemical analyses, and macroscopic and microscopic histopathology were evaluated. No adverse effects were observed after the administration of the different doses of the hydroxytyrosol-rich VOO extract, which suggests that the enrichment of VOO in its phenolic compound is safe, and can be used as functional foods for the treatment of chronic degenerative diseases.


Assuntos
Azeite de Oliva/toxicidade , Álcool Feniletílico/análogos & derivados , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Testes de Toxicidade Subcrônica , Animais , Feminino , Masculino , Nível de Efeito Adverso não Observado , Álcool Feniletílico/toxicidade , Ratos Wistar , Medição de Risco , Fatores de Tempo
10.
Ulus Travma Acil Cerrahi Derg ; 25(5): 433-439, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31475327

RESUMO

BACKGROUND: Pulmonary contusion (PC) is an important life-threatening clinical condition characterized by lung injury and inflammation. Caffeic acid phenethyl ester (CAPE) is a biological agent with potent antioxidant and anti-inflammatory effects. This study aimed to investigate the potential effects of CAPE on tissue damage, nuclear factor kappa-beta (Nf-κß) activity, inducible nitric oxide synthase (iNOS) synthesis, and pulmonary apoptosis in an experimental PC model. METHODS: Forty adult Wistar albino rats were used in this study and divided into four groups as follows: control, PC, PC + CAPE, and CAPE. CAPE was administered intraperitoneally for seven days following PC formation (10 µmol/kg, dissolved in dimethyl sulfoxide). Wet/dry weight ratio in lung tissue was determined. The pulmonary tissue was examined using hematoxylin-eosin and Masson's trichrome histochemical staining and also by scanning electron microscopy. Nf-κß and iNOS activities in the lungs were determined by the indirect immunohistochemical method. Pulmonary apoptosis was detected by the TUNEL method. RESULTS: Increased leukocyte infiltration score, pulmonary edema, alveolar damage, and increased Nf-κß and iNOS activities were determined in the PC group. CAPE administration inhibited Nf-κß and iNOS activities and pulmonary apoptosis. CONCLUSION: In this study, the findings showed that CAPE inhibited tissue damage by suppressing inflammatory mediators of Nf-κß and iNOS activities. Also, CAPE was found to be protective in the lung tissue and could be used as a therapeutic agent.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Lesão Pulmonar/metabolismo , NF-kappa B/metabolismo , Álcool Feniletílico/análogos & derivados , Pneumonia/metabolismo , Animais , Álcool Feniletílico/farmacologia , Ratos , Ratos Wistar
11.
Molecules ; 24(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31492013

RESUMO

Hydroxytyrosol and two other polyphenols of olive tree, hydroxytyrosol acetate and 3,4-dihydroxyphenylglycol, are known for a wide range of beneficial activities in human health and prevention from diseases. The inability to isolate high, pure amounts of these natural compounds and the difficult and laborious procedures for the synthesis of them led us to describe herein an efficient, easy, cheap, and scaling up synthetic procedure, from catechol, via microwave irradiation.


Assuntos
Técnicas de Química Sintética , Metoxi-Hidroxifenilglicol/análogos & derivados , Álcool Feniletílico/análogos & derivados , Técnicas de Química Sintética/métodos , Humanos , Metoxi-Hidroxifenilglicol/síntese química , Metoxi-Hidroxifenilglicol/química , Estrutura Molecular , Álcool Feniletílico/síntese química , Álcool Feniletílico/química
12.
Nutrients ; 11(8)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394805

RESUMO

Olive oil is one of the main ingredients in the Mediterranean diet, being an important ally in disease prevention. Its nutritional composition is comprised of mainly monounsaturated fatty acids, with oleic being the major acid, plus minor components which act as effective antioxidants, such as hydroxytyrosol. Studies have shown that the consumption of olive oil, as well as its isolated components or in synergism, can be a primary and secondary protective factor against the development of cardiovascular diseases since it reduces the concentrations of low-density lipoproteins and increases the concentration of high-density lipoproteins. Furthermore, it exerts an influence on the inflammatory markers, such as interleukin-6 and tumor necrosis factor, which are pro-inflammatory agents in the body. The components present in olive oil are also associated with the promotion of intestinal health since they stimulate a higher biodiversity of beneficial gut bacteria, enhancing their balance. The objective of this review is to present recent data on investigated effects of olive oil and its components on the metabolism, focused on cardiovascular diseases, inflammation, and gut biota.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Inflamação/prevenção & controle , Azeite de Oliva/administração & dosagem , Azeite de Oliva/química , Adulto , Biomarcadores/sangue , Dieta Mediterrânea , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamação/sangue , Lipoproteínas LDL/sangue , Ácido Oleico/administração & dosagem , Fenóis/administração & dosagem , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/análogos & derivados
13.
Int J Mol Med ; 44(4): 1531-1540, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31432093

RESUMO

Advanced oxidation protein products (AOPPs) can trigger NADPH oxidase (NOX) and lead to the production of reactive oxygen species (ROS) in the pathophysiology of rheumatoid arthritis (RA). Hydroxytyrosol (HT) is a phenolic composite in olive oil that has antioxidant and anti­inflammatory effects and enhances autophagy. Early research has revealed that HT can activate the silent information regulator 1 (SIRT1) pathway to induce autophagy and alleviate the cartilage inflammatory response caused by H2O2. However, whether HT can attenuate AOPP­induced NOX and inflammatory responses remains to be elucidated. The present study aimed to investigate how HT can alleviate the damage caused by AOPPs. In cell experiments, chondrocytes were pre­stimulated with HT and then exposed to AOPPs. First, it was found that HT promoted autophagy through the SIRT1 pathway, increased the expression of autophagy­related proteins including microtubule­associated protein 1 light chain 3, autophagy related (ATG)5 and ATG7, and decreased the expression of P62. Furthermore, HT reduced the expression of NOX, which was affected by AOPPs in chondrocytes through the SIRT1 pathway. Finally, the expression of inflammatory cytokines caused by AOPPs was downregulated following HT treatment. In conclusion, it was found that HT reduced the expression of NOX and inhibited the inflammatory response caused by AOPPs in chondrocytes through the SIRT1 pathway.


Assuntos
Produtos da Oxidação Avançada de Proteínas/farmacologia , Autofagia/efeitos dos fármacos , Inflamação/etiologia , Inflamação/metabolismo , NADPH Oxidases/metabolismo , Álcool Feniletílico/análogos & derivados , Sirtuína 1/genética , Animais , Animais Recém-Nascidos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Regulação da Expressão Gênica , Inflamação/patologia , Interleucina-6/biossíntese , Metaloproteinase 13 da Matriz/biossíntese , Oxirredução/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Interferência de RNA , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
14.
Biol Pharm Bull ; 42(10): 1689-1693, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31366853

RESUMO

Caffeic acid phenethyl ester (CAPE), an active polyphenolic component of honeybee propolis, has been demonstrated to have many medicinal properties. However, the antitumor effect and mechanism of CAPE on laryngeal carcinoma cells have not been examined. In this study, we treated HEp2 cells with various concentration of CAPE, and the results showed that CAPE can reduce the viability of HEp2 cells with IC50 values of 23.8 ± 0.7 µM for 72 h. Meanwhile, CAPE significantly inhibited activation of signal transducer and activator of transcription (Stat)3 in a concentration dependent manner in HEp2 cells and regulated the expression and transcription of Plk1. AG490, a specific Stat3 inhibitor, not only inhibited the activation and expression of Stat3, but also inhibited the expression of Plk1 in HEp2 cells, so Stat3 was probably involved in the regulation of Plk1 in HEp2 cells. In addition, treatment of CAPE leaded to a blockage of cell cycle in S phase in HEp2 cells. Therefore, CAPE inhibited the proliferation of HEp2 Cells probably by regulating Stat3/Plk1 pathway and inducing S phase arrest.


Assuntos
Ácidos Cafeicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Neoplasias Laríngeas/metabolismo , Álcool Feniletílico/análogos & derivados , Própole/química , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Fase S/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Laríngeas/tratamento farmacológico , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Polifenóis/farmacologia , Polifenóis/uso terapêutico
15.
Biol Pharm Bull ; 42(7): 1120-1127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257288

RESUMO

Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1ß, resulting in reduced nitric oxide and prostaglandin E2 production. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Edema/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Úlcera Gástrica/tratamento farmacológico , Estômago/efeitos dos fármacos , Animais , Aspirina , Carragenina , Celecoxib , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Indometacina , Masculino , Olea , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Ratos Sprague-Dawley , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo
16.
Nutrients ; 11(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284510

RESUMO

Maternal supplementation with hydroxytyrosol, a polyphenol present in olive leaves and fruits, is a highly promising strategy to improve the oxidative and metabolic status of fetuses at risk of intrauterine growth restriction, which may diminish the appearance of low-birth-weight neonates. The present study aimed to determine whether hydroxytyrosol, by preventing lipid peroxidation, may influence the fat accretion and energy homeostasis in the liver, as well as the fatty acid composition in the liver and muscle. The results indicate that hydroxytyrosol treatment significantly decreased the energy content of the fetal liver, without affecting fat accretion, and caused significant changes in the availability of fatty acids. There were significant increases in the amount of total polyunsaturated fatty acids, omega-3 and omega-6, which are highly important for adequate fetal tissue development. However, there were increases in the omega-6/omega-3 ratio and the desaturation index, which make further studies necessary to determine possible effects on the pro/anti-inflammatory status of the fetuses.


Assuntos
Adiposidade/efeitos dos fármacos , Suplementos Nutricionais , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/metabolismo , Retardo do Crescimento Fetal/prevenção & controle , Feto/efeitos dos fármacos , Fígado/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Animais , Modelos Animais de Doenças , Feminino , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/fisiopatologia , Feto/metabolismo , Feto/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/fisiopatologia , Exposição Materna , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Álcool Feniletílico/farmacologia , Gravidez , Sus scrofa
17.
Oxid Med Cell Longev ; 2019: 4101738, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281574

RESUMO

Oxidative stress (OS) induces osteoblast apoptosis, which plays a crucial role in the initiation and progression of osteoporosis. Although OS is closely associated with mitochondrial dysfunction, detailed mitochondrial mechanisms underlying OS-induced osteoblast apoptosis have not been thoroughly elucidated to date. In the present study, we found that mitochondrial abnormalities largely contributed to OS-induced osteoblast apoptosis, as evidenced by enhanced production of mitochondrial reactive oxygen species; considerable reduction in mitochondrial respiratory chain complex activity, mitochondrial membrane potential, and adenosine triphosphate production; abnormality in mitochondrial morphology; and alteration of mitochondrial dynamics. These mitochondrial abnormalities were primarily mediated by an imbalance in mitochondrial fusion and fission through a protein kinase B- (AKT-) glycogen synthase kinase 3ß- (GSK3ß-) optic atrophy 1- (OPA1-) dependent mechanism. Hydroxytyrosol (3,4-dihydroxyphenylethanol (HT)), an important compound in virgin olive oil, significantly prevented OS-induced osteoblast apoptosis. Specifically, HT inhibited OS-induced mitochondrial dysfunction by decreasing OPA1 cleavage and by increasing AKT and GSK3ß phosphorylation. Together, our results indicate that the AKT-GSK3ß signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage, which may contribute to OS-induced osteoblast apoptosis. Moreover, our results suggest that HT could be an effective nutrient for preventing osteoporosis development.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Mitocôndrias/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoporose/metabolismo , Álcool Feniletílico/análogos & derivados , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Osteoblastos/patologia , Osteoporose/patologia , Estresse Oxidativo/fisiologia , Álcool Feniletílico/farmacologia , Transdução de Sinais , Transfecção
18.
Molecules ; 24(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269664

RESUMO

Τoward a harmonized and standardized procedure for the determination of total hydroxytyrosol and tyrosol content in virgin olive oil (VOO), the pros of a recently published in house validated ultra high performance liquid chromatography (UHPLC) protocol are discussed comparatively with those of other procedures that determine directly or indirectly the compounds hosted under the health claim on "olive oil polyphenols" (EC regulation 432/2012). Authentic VOOs were analyzed with five different liquid chromatographic separation protocols and 1H-NMR one in five different laboratories with expertise in VOO phenol analysis within three months. Data comparison indicated differences in absolute values. Method comparison using appropriate tools (Passing-Bablok regression and Bland Altman analyses) for all protocols vs. the UHPLC one indicated slight or statistically significant differences. The results were also discussed in terms of cost effectiveness, detection means, standard requirements and ways to calculate the total hydroxytyrosol and tyrosol content. Findings point out that the in-house validated fit for the purpose UHPLC protocol presents certain pros that should be exploited by the interested parties. These are the simplicity of sample preparation, fast elution time that increase the number of samples analyzed per day and integration of well-resolved peaks with the aid of only two commercially available external standards. Importance of correction factors in the calculations is stressed.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Azeite de Oliva/química , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/análise , Espectroscopia de Prótons por Ressonância Magnética , Padrões de Referência
19.
J Biochem Mol Toxicol ; 33(9): e22377, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332898

RESUMO

Hydroxytyrosol (HT), a primary phenolic antioxidant in olive oil, can afford protection from oxidative stress (OS) in different cells, including skin cells. In particular, it regulates several inflammation-associated processes as well as in improving the antioxidant defense system. However, there is no information about HT used in the treatment of hair loss. This work aimed at exploring the potential protective actions of HT against OS in rat dermal papilla cells. After treatment, the related expression of protein and messenger RNA were detected using morphological and molecular analyses. The results showed that HT significantly reduced intracellular reactive oxygen species level, apoptotic markers and inflammation induced by OS and enhanced cell survival by regulating autophagy. Furthermore, HT enhanced the secretion of hair growth factors in the anti-inflammation process. These results suggest that HT has a significant protective ability against OS and encourage the use of this biological ingredient as a possible tool to prevent alopecia.


Assuntos
Antioxidantes/farmacologia , Autofagia/efeitos dos fármacos , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Pele/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Álcool Feniletílico/farmacologia , Ratos , Pele/citologia
20.
Food Funct ; 10(8): 4897-4910, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31339147

RESUMO

Hydroxytyrosol (HT) is involved in healthful activities and is beneficial to lipid metabolism. Many investigations focused on finding tissue-specific targets of HT through the use of different omics approaches such as transcriptomics and proteomics. However, it is not clear which (if any) of the potential molecular targets of HT reported in different studies are concurrently affected in various tissues. Following the bioinformatic analyses of publicly available data from a selection of in vivo studies involving HT-supplementation, we selected differentially expressed lipid metabolism-related genes and proteins common to more than one study, for validation in rodent liver samples from the entire selection. Four miRNAs (miR-802-5p, miR-423-3p, miR-30a-5p, and miR-146b-5p) responded to HT supplementation. Of note, miR-802-5p was commonly regulated in the liver and intestine. Our premise was that, in an organ crucial for lipid metabolism such as the liver, consistent modulation should be found for a specific target of HT even if different doses and duration of HT supplementation were used in vivo. Even though our results show inconsistency regarding differentially expressed lipid metabolism-related genes and proteins across studies, we found Fgf21 and Rora as potential novel targets of HT. Omics approaches should be fine-tuned to better exploit the available databases.


Assuntos
Álcool Feniletílico/análogos & derivados , Proteínas/genética , Biologia Computacional , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , MicroRNAs/metabolismo , Álcool Feniletílico/farmacologia , Proteínas/metabolismo , Proteômica
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