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1.
Food Chem ; 349: 129154, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33556721

RESUMO

Caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) are bioactive molecules with poor solubility. We investigated the interaction between CA/CAPE and micellar casein (MC), and the physico-chemical and antioxidant properties of the complexes. Fluorescence spectroscopy analysis showed that both CA and CAPE formed complexes with MC via hydrophobic interactions. The binding constant was higher for CAPE than for CA at each temperature. The complexes were confirmed by FTIR and XRD. The secondary structure of MC was not affected by CAPE, but its morphology changed. CA/CAPE did not induce the dissociation of casein micelles. CA and CAPE increased and decreased, respectively, the bulk and tapped densities of MC. The complexes had higher thermal stability and DPPH radical scavenging capacity than free MC or CA/CAPE.


Assuntos
Ácidos Cafeicos/química , Caseínas/química , Micelas , Álcool Feniletílico/análogos & derivados , Antioxidantes/química , Interações Hidrofóbicas e Hidrofílicas , Álcool Feniletílico/química , Ligação Proteica , Estrutura Secundária de Proteína , Solubilidade
2.
Viruses ; 13(2)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540713

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Although measures to control SARS-CoV-2, namely, vaccination, medication, and chemical disinfectants are being investigated, there is an increase in the demand for auxiliary antiviral approaches using natural compounds. Here we have focused on hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX®) and evaluated its SARS-CoV-2-inactivating activity in vitro. We showed that the HIDROX solution exhibits time- and concentration-dependent SARS-CoV-2-inactivating activities, and that HIDROX has more potent virucidal activity than pure HT. The evaluation of the mechanism of action suggested that both HIDROX and HT induced structural changes in SARS-CoV-2, which changed the molecular weight of the spike proteins. Even though the spike protein is highly glycosylated, this change was induced regardless of the glycosylation status. In addition, HIDROX or HT treatment disrupted the viral genome. Moreover, the HIDROX-containing cream applied on film showed time- and concentration-dependent SARS-CoV-2-inactivating activities. Thus, the HIDROX-containing cream can be applied topically as an antiviral hand cream. Our findings suggest that HIDROX contributes to improving SARS-CoV-2 control measures.


Assuntos
Antivirais/farmacologia , Olea , Álcool Feniletílico/análogos & derivados , Extratos Vegetais/farmacologia , /efeitos dos fármacos , Administração Tópica , Animais , Antivirais/química , Carboidratos/química , Chlorocebus aethiops , Genoma Viral/efeitos dos fármacos , Glicosilação , Testes de Sensibilidade Microbiana , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/farmacologia , Fosfoproteínas/química , Extratos Vegetais/química , /fisiologia , Creme para a Pele , Glicoproteína da Espícula de Coronavírus/química , Células Vero , Inativação de Vírus/efeitos dos fármacos
3.
Molecules ; 26(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430068

RESUMO

Cutaneous melanoma is the deadliest type of skin cancer, characterized by a high molecular and metabolic heterogeneity which contributes to therapy resistance. Despite advances in treatment, more efficient therapies are needed. Olive oil compounds have been described as having anti-cancer properties. Here, we clarified the cytotoxic potential of oleic acid, homovanillyl alcohol, and hydroxytyrosol on melanoma cells. Metabolic viability was determined 48 h post treatment of A375 and MNT1 cells. Metabolic gene expression was assessed by qRT-PCR and Mitogen-Activated Protein Kinase (MAPK) activation by Western blot. Hydroxytyrosol treatment (100 and 200 µM) significantly reduced A375 cell viability (p = 0.0249; p < 0.0001) which, based on the expression analysis performed, is more compatible with a predominant glycolytic profile and c-Jun N-terminal kinase (JNK) activation. By contrast, hydroxytyrosol had no effect on MNT1 cell viability, which demonstrates an enhanced oxidative metabolism and extracellular signal-regulated kinase (ERK) activation. This compound triggered cell detoxification and the use of alternative energy sources in A375 cells, inhibiting JNK and ERK pathways. Despite oleic acid and homovanillyl alcohol demonstrating no effect on melanoma cell viability, they influenced the MNT1 glycolytic rate and A375 detoxification mechanisms, respectively. Both compounds suppressed ERK activation in MNT1 cells. The distinct cell responses to olive oil compounds depend on the metabolic and molecular mechanisms preferentially activated. Hydroxytyrosol may have a cytotoxic potential in melanoma cells with predominant glycolytic metabolism and JNK activation.


Assuntos
Antineoplásicos Fitogênicos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanoma , Azeite de Oliva/química , Álcool Feniletílico/análogos & derivados , Neoplasias Cutâneas , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Reprogramação Celular , Humanos , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Melanoma/patologia , Proteínas de Neoplasias/metabolismo , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
4.
Food Chem ; 337: 127996, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919275

RESUMO

Hydroxytyrosol oligomer prepared by bioenzyme shows stronger health-promoting properties than its monomer. However, the polymerization process carried out by laccase, tyrosinase or horseradish peroxidase is still lacking in term of product characterization, kinetics and thermodynamics. To achieve these aspects, ATR-FT-IR, NMR, the Michaelis-Menten equation and isothermal titration calorimetry were explored. The results showed that the identified polymers presented a CC bond and a degree of polymerization less than six. Laccase showed the greatest affinity to hydroxytyrosol via comparison of Km and Vm. All of these polymerization processes were spontaneous and exothermic behaviuors ranging from 30 to 50 °C, and were driven by hydrogen bonds, van der Waals interactions and hydrophobic interactions. Furthermore, circular dichroism spectroscopy was used to reveal the enzymatic structural changes during the catalysis, which showed that ß-sheet levels for laccase, α-helix levels for tyrosinase, and the α-helix and random coil levels for horseradish peroxidase were dramatically decreased.


Assuntos
Catecol Oxidase/metabolismo , Peroxidase do Rábano Silvestre/metabolismo , Polimerização , Calorimetria/métodos , Catálise , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Lacase/metabolismo , Oxirredução , Álcool Feniletílico/análogos & derivados , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
5.
Food Chem ; 345: 128468, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33341300

RESUMO

Antioxidant interactions of γ-terpinene with α-tocopherol mimic 2,2,5,7,8-pentamethyl-6-chromanol (PMHC) and caffeic acid phenethyl ester (CAPE), used as models, respectively, of mono- and poly-phenols were demonstrated by differential oximetry during the inhibited autoxidation of model substrates: stripped sunflower oil, squalene, and styrene. With all substrates, γ-terpinene acts synergistically regenerating the chain-breaking antioxidants PMHC and CAPE from their radicals, via the formation of hydroperoxyl radicals. The inhibition duration for mixtures PMHC/γ-terpinene and CAPE/γ-terpinene increased with γ-terpinene concentration, while rate constants for radical-trapping were unchanged by γ-terpinene, being 3.1 × 106 and 4.8 × 105 M-1s-1 for PMHC and CAPE in chlorobenzene (30 °C). Using 3,5-di-tert-butylcatechol and 3,5-di-tert-butyl-1,2-bezoquinone we demonstrate that γ-terpinene can reduce quinones to catechols enabling their antioxidant activity. The different synergy mechanism of γ-terpinene with mono- and poly-phenolic antioxidants is discussed and its relevance is proven in homogenous lipids using natural α-tocopherol and hydroxytyrosol as antioxidants, calling for further studies in heterogenous food products.


Assuntos
Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/farmacologia , Peróxidos/química , Fenóis/química , Fenóis/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Cromanos/química , Cromanos/farmacologia , Sinergismo Farmacológico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia
6.
Ecotoxicol Environ Saf ; 207: 111578, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254423

RESUMO

Cadmium (Cd), an environmental pollutant, is evidenced to cause hepatotoxicity. In this study, the potential protective effect of caffeic acid phenethyl ester (CAPE) on cadmium-induced liver damage was investigated. Forty male mice were treated daily with either CdCl2 (1.5 mg/kg body weight (b.w.), gavage) or CAPE (10 µmol/kg b.w., gavage) or both for 4 weeks. CAPE administration significantly reduced Cd level and liver and body weight, and increased AST, ALT and ALP level. Moreover, CAPE prevented CdCl2-induced oxidative stress via PI3K/Akt/mTOR pathway and inhibited apoptosis by regulating apoptosis markers. CAPE also suppressed the CdCl2-induced inflammation by reducing the inflammatory mediators, including TNF-α, IL-6 and IL-1ß. Furthermore, CAPE alleviated CdCl2-induced reduction of TLR4. It should be noted that this effect was achieved by targeting miR-182-5p, and CAPE improved miR-182-5p level. The improvement of the liver tissue histopathology by CAPE confirmed the biochemical data. These results show for the first time that miR-182-5p/TLR4 axis involved in CAPE's protection against CdCl2-induced hepatotoxicity, and may provide novel insights into the treatment of cadmium-related diseases.


Assuntos
Cádmio/toxicidade , Ácidos Cafeicos/farmacologia , Poluentes Ambientais/toxicidade , Álcool Feniletílico/análogos & derivados , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Inflamação , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , MicroRNAs/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Papel (figurativo) , Receptor 4 Toll-Like/metabolismo
7.
Food Chem ; 335: 127576, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739805

RESUMO

The main causes of food spoilage come from the process of oxidation and the contamination by microorganisms. For the purpose of increasing food shelf-life the industries employ different techniques, being the addition of preservatives, one of the most used. The aim of this contribution was to investigate the potential antioxidant properties of tyrosol (4-hydroxyphenethyl alcohol, 4-OH) and tyrosol derived isomers (2-hydroxyphenethyl alcohol, 2-OH and 3-hydroxyphenethyl alcohol, 3-OH) against reactive oxygen species (ROS) and the antimicrobial effect on Staphylococcus aureus and Escherichia coli. Furthermore, the type of antioxidant effect of substrates and commercial antioxidants mixtures was studied. Upon visible-light, the substrates interacted with the vitamin B2 and different ROS were generated. All the compounds deactivated O2(1Δg) and O2●-, whereas only 2-OH and 3-OH inhibited H2O2 and HO●. The substrates exhibited a synergistic antioxidant effect when combined with commercial antioxidants. 2-OH showed antimicrobial activity against strains tested.


Assuntos
Aditivos Alimentares/farmacologia , Álcool Feniletílico/análogos & derivados , Riboflavina/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Sinergismo Farmacológico , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia
8.
Food Chem ; 336: 127730, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768900

RESUMO

Phenols are responsible for the only health claim of virgin olive oil (VOO) recognized by the European Commission EU 432/2012 and the European Food Safety Authority. In this research, we studied the decrease in the phenolic content of 160 extra VOOs (EVOOs) after 12 months storage in darkness at 20 °C. Phenolic concentration was decreased 42.0 ± 24.3% after this period and this reduction strongly depended on the initial phenolic profile. Hence, EVOOs with predominance in oleacein and oleocanthal experienced a larger decrease in phenolic content than oils enriched in other phenols. Complementarily, hydroxytyrosol and oleocanthalic acid increased significantly in aged EVOOs, which allowed their discrimination from recently produced EVOOs. These changes are explained by degradation of main secoiridoids during storage due to their antioxidant properties. Hydroxytyrosol and oleocanthalic acid can be considered markers of olive oil ageing, although they can also provide information about quality or stability.


Assuntos
Armazenamento de Alimentos/métodos , Azeite de Oliva/química , Fenóis/química , Antioxidantes/química , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Iridoides/análise , Fenóis/análise , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/análise , Curva ROC , Espectrometria de Massas em Tandem , Fatores de Tempo
9.
Food Chem ; 336: 127674, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32781353

RESUMO

Dried flower buds of Japanese sophora (Sophora japonica) comprising rutinosidase activity were tested in rutinosylation of tyrosol via transglycosylation process from rutin. Optimal conditions for transrutinosylation of tyrosol were 49 mM rutin and 290 mM tyrosol, giving maximum conversion up to 66.4% and 24% yield of isolated and purified rutinoside. The rutinosylation proceeded exclusively on the primary hydroxyl of tyrosol, thus forming rhamnosylated derivative of salidroside. This strict regioselectivity differentiates the sophora biocatalyst from microbial rutinosidases.


Assuntos
Flores/química , Álcool Feniletílico/análogos & derivados , Sophora/química , Flores/metabolismo , Glucosídeos/química , Glucosídeos/metabolismo , Glicosilação , Fenóis/química , Fenóis/metabolismo , Álcool Feniletílico/química , Álcool Feniletílico/metabolismo , Rutina/química , Rutina/metabolismo
10.
Acta Biomed ; 91(13-S): e2020009, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33170175

RESUMO

BACKGROUND AND AIM OF THE WORK: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics of coronavirus disease. This virus is able to attack the cells of the airway epithelium by binding to the transmembrane angiotensin I converting enzyme 2 (ACE2). We developed an oral spray that could inhibit the SARS-CoV-2 endocytosis. The spray contains hydroxytyrosol for its anti-viral, anti-inflammatory and anti-oxidant properties, and α-cyclodextrin for its ability to deplete sphingolipids, that form the lipid rafts where ACE2 localizes. The aim of the present pilot multi-centric open non-controlled observational study was to evaluate the safety profile of the "Endovir Stop" spray. METHODS: An MTT test was performed to evaluate cytotoxicity of the spray in two human cell lines. An oxygen radical absorbance capacity assay was performed to evaluate the antioxidant capacity of the spray. The spray was also tested on 87 healthy subjects on a voluntary basis. RESULTS: The MTT test revealed that the spray is not cytotoxic. The ORAC assay showed a good antioxidant capacity for the spray. Endovir Stop tested on healthy volunteers showed the total absence of side effects and drug interactions during the treatment. CONCLUSIONS: We demonstrated that Endovir Stop spray is safe. The next step would be the administration of the efficacy of the spray by testing it to a wider range of people and see whether there is a reduced infection rate of SARS-CoV-2 in the treated subjects than in the non-treated individuals.


Assuntos
Antivirais/efeitos adversos , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Endocitose/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Pneumonia Viral/tratamento farmacológico , alfa-Ciclodextrinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Células CACO-2 , Técnicas de Cultura de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Orais , Pandemias , Álcool Feniletílico/efeitos adversos , Projetos Piloto , Adulto Jovem
11.
Acta Biomed ; 91(13-S): e2020022, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33170176

RESUMO

BACKGROUND AND AIM OF THE WORK: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemics. This virus attacks the cells by binding to the transmembrane angiotensin I converting enzyme 2. In this study, we experimented a food supplement containing alpha-cyclodextrin and hydroxytyrosol for the improvement of the defenses against the SARS-CoV-2. Hydroxytyrosol has anti-viral properties and is able to reduce the serum lipids in mice. α-cyclodextrin has the ability to deplete sphingolipids and phospholipids from the cellular membranes. The aim of the present preliminary open non-controlled interventional study was to evaluate the efficacy of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. METHODS: Fifty healthy volunteers at a higher risk of SARS-CoV-2 infection from Northern Cyprus and six positive individuals for SARS-CoV-2 were enrolled in this study. The in silico prediction was performed using D3DOCKING to evaluate the interactions of hydroxytyrosol and alpha-cyclodextrin with proteins involved in the SARS-CoV-2 endocytosis. RESULTS: The 50 volunteers did not become positive in 15 days for SARS-CoV-2 after the administration of the compound for two weeks, despite they were at higher risk of infection than the general population. Interestingly, in the cohort of six positive patients, two patients were administered the spray and became negative after five days, despite the viral load was higher in the treated subjects than the untreated patients who became negative after ten days. In addition, we identified possible interactions among hydroxytyrosol and alpha-cyclodextrin with the protein Spike and the human proteins ACE2 and TMPRSS2. CONCLUSIONS: We reported on the results of the possible role of alpha-cyclodextrin and hydroxytyrosol in improving defenses against SARS-CoV-2. The next step will be the administration of the compound to a larger cohort in a controlled study to confirm the reduction of the infection rate of SARS-CoV-2 in the treated subjects.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Pandemias/prevenção & controle , Álcool Feniletílico/análogos & derivados , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , alfa-Ciclodextrinas/uso terapêutico , Adulto , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Chipre , Endocitose/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Orais , Álcool Feniletílico/uso terapêutico , Projetos Piloto , Pneumonia Viral/diagnóstico , Carga Viral
12.
Artigo em Inglês | MEDLINE | ID: mdl-32575426

RESUMO

Recent advances in phytomedicine have explored some potential candidates for nerve regeneration, including hydroxytyrosol (HT). This study was undertaken to explore the potential effects of HT on human Schwann cells' proliferation. Methods: The primary human Schwann cell (hSC) was characterized, and the proliferation rate of hSC supplemented with various concentrations of HT was determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle analysis and protein expression of glial fibrillary acidic protein (GFAP) and p75 nerve growth factor receptor (p75 NGFR) were evaluated via the immunofluorescence technique. Results: In vitro culture of hSCs revealed spindle-like, bipolar morphology with the expression of specific markers of hSC. Hydroxytyrosol at 10 and 20 ng/mL significantly increased the proliferation of hSCs by 30.12 ± 5.9% and 47.8 ± 6.7% compared to control (p < 0.05). Cell cycle analysis showed that HT-treated hSCs have a higher proliferation index (16.2 ± 0.2%) than the control (12.4 ± 0.4%) (p < 0.01). In addition, HT significantly increased the protein expression of GFAP and p75NGFR (p < 0.05). Conclusion: HT stimulates the proliferation of hSCs in vitro, indicated by a significant increase in the hSC proliferation index and protein expression of hSCs' proliferation markers, namely p75 NGFR and GFAP.


Assuntos
Antioxidantes , Proliferação de Células , Regeneração Nervosa , Álcool Feniletílico/análogos & derivados , Células de Schwann , Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Regeneração Nervosa/efeitos dos fármacos , Álcool Feniletílico/farmacologia , Células de Schwann/efeitos dos fármacos
13.
J Oleo Sci ; 69(7): 677-684, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32522947

RESUMO

A simple screening method for discrimination between commercial extra virgin olive oils and their blends with other vegetable oils was developed. Squalene, which was contained relatively high amounts in virgin olive oil, was determined by HPLC after a simple pretreatment that was carried out by dilution of oil samples with 2-propanol. Tyrosol, which was contained at relatively high concentration in virgin olive oil among phenolic compounds, was determined by HPLC after a simple liquid-liquid extraction. When using squalene and tyrosol contents as axes, extra virgin olive oils could be discriminated from pure olive oils, blended oils (extra virgin olive oils with sunflower oil or grapeseed oil) and other vegetable oils. These results suggest that determining squalene and tyrosol in seed oil samples could be useful in distinguishing between extra virgin olive oil and blended oils as a screening method.


Assuntos
Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Qualidade dos Alimentos , Azeite de Oliva/análise , Azeite de Oliva/química , Álcool Feniletílico/análogos & derivados , Esqualeno/análise , Cromatografia Líquida de Alta Pressão , Extração Líquido-Líquido/métodos , Álcool Feniletílico/análise , Óleos Vegetais/análise
14.
J Adhes Dent ; 22(3): 285-296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32435769

RESUMO

PURPOSE: To investigate the long-term effect of 0.05% or 0.1% caffeic acid phenethyl ester (CAPE) on dentin matrix stability and hybrid layer stability, using an etch-and-rinse (Adper Scotchbond Multipurpose/ASB) or a self-etch adhesive (Clearfil SE Bond/CSE). MATERIALS AND METHODS: Dentin matrix specimens were assigned to five groups: 0.05% or 0.1% CAPE, green tea (GT), and the controls distilled water (DW) and dimethyl sulfoxide (DMSO). Following immersion of specimens for 1 h, modulus of elasticity (ME) and dentin mass change (MG) were determined at 3 post-treatment time points: immediately afterwards and at 3 and 6 months. Collagen solubilization (CS) was estimated by hydroxyproline (HYP) quantification. Resin-dentin interfaces with both adhesives were assessed with in situ zymography tests to evaluate gelatinolytic activity (GA). The dentin pretreatments were actively applied for 60 s. The sealing ability of aged resin-bonded slices was assessed by nanoleakage tests. RESULTS: GT increased immediate ME, which decreased significantly after 3 months (p < 0.0001). The CAPE groups did not differ from the control groups. GT provided a significant increase in dentin matrix mass after treatment (p < 0.0001). No significant differences regarding MG were observed for CAPE 0.1%, CAPE 0.05%, DW, and DMSO groups after 3 and 6 months. Cumulative HYP release revealed that CAPE groups and GT were statistically similar to DW and DMSO; the GT group exhibited statistically significantly less HYP release than did CAPE groups (p = 0.0073). Treatment with 0.05% or 0.1% CAPE presented lower GA when applied to ASB before acid conditioning (p < 0.05), but no differences were detected when the CAPE groups were applied to CSE. CAPE at 0.1% significantly reduced nanoleakage for CSE, and 0.05% CAPE with CSE presented levels of nanoleakage similar to those of the CSE control group. CONCLUSION: CAPE at 0.05% or 0.01% did not influence ME, MG, or CS, but reduced GA when applied to ASB before acid conditioning. CAPE at 0.1% with CSE promoted adhesive layer integrity.


Assuntos
Colagem Dentária , Adesivos Dentinários , Ácidos Cafeicos , Cimentos Dentários , Dentina , Teste de Materiais , Álcool Feniletílico/análogos & derivados , Resistência à Tração
15.
Adv Exp Med Biol ; 1195: 77-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468462

RESUMO

Neurodegenerative diseases lead to the death of nerve cells in the brain or the spinal cord. A wide range of diseases are included within the group of neurodegenerative disorders, with the most common ones being dementia, Alzheimer's, and Parkinson's diseases. Millions of older people are suffering from such pathologies. The global increase of life expectancy unavoidably leads to a consequent increase in the number of people who will be at some degree affected by neurodegenerative-related diseases. At this moment, there is no effective therapy or treatment that can reverse the loss of neurons. A growing number of studies highlight the value of the consumption of medical foods, and in particular olive oil, as one of the most important components of the Mediterranean diet. A diet based on extra virgin olive oil seems to contribute toward the lowering of risk of age-related pathologies due to high phenol concentration. The link of a polyphenol found in extra virgin olive oil, namely, tyrosol, with the protein tyrosinase, associated to Parkinson's disease is underlined as a paradigm of affiliation between polyphenols and neurodegenerative disorders.


Assuntos
Doenças Neurodegenerativas/prevenção & controle , Azeite de Oliva/química , Azeite de Oliva/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Dieta Mediterrânea , Humanos , Doenças Neurodegenerativas/dietoterapia , Azeite de Oliva/uso terapêutico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Polifenóis/uso terapêutico
16.
Ecotoxicol Environ Saf ; 197: 110610, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298858

RESUMO

Cadmium pollution and poisoning are serious environmental and pharmacological concerns, and effective drugs can alleviate or offset cadmium-induced toxicity are badly needed. In this study, Caffeic acid phenethyl ester (CAPE), a major active component of propolis, showed protective effect against CdCl2-induced toxicology by suppressing autophagy in HepG2 cells. CircRNAs are increasingly perceived as vital regulators in the process of autophagy. However, it remain unclear whether circRNAs are involved in CAPE's protection against CdCl2-induced autophagy. Under this context, the roles of CircRNA (hsa_circ_0040768) in CAPE's protection against CdCl2-induced damage were investigated by PCR and Western blot. Results showed that CAPE significantly (P < 0.05) increased cell viability via inhibiting CdCl2-induced autophagy, and this process was regulated by hsa_circ_0040768/MAP1LC3B axis. Overexpressing hsa_circ_0040768 led to reduced cell viability and increased autophagy in CAPE-treated HepG2 cells exposed to CdCl2. In contrast, silencing hsa_circ_0040768 showed similar protective effect to CAPE. These results show for the first time the involvement of the hsa_circ_0040768/MAP1LC3B axis in the CAPE's protection against CdCl2-induced autophagy, and provide novel insights into the pathogenesis and potential prevention/treatment of cadmium-associated diseases.


Assuntos
Autofagia/efeitos dos fármacos , Cádmio/toxicidade , Ácidos Cafeicos/farmacologia , Poluentes Ambientais/toxicidade , Álcool Feniletílico/análogos & derivados , RNA Circular/metabolismo , Autofagia/genética , Células Hep G2 , Humanos , Álcool Feniletílico/farmacologia
17.
Int J Mol Sci ; 21(7)2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32276415

RESUMO

Numerous studies highlighted the beneficial effects of the Mediterranean diet (MD) in maintaining health, especially during ageing. Even neurodegeneration, which is part of the natural ageing process, as well as the foundation of ageing-related neurodegenerative disorders like Alzheimer's and Parkinson's disease (PD), was successfully targeted by MD. In this regard, olive oil and its polyphenolic constituents have received increasing attention in the last years. Thus, this study focuses on two main olive oil polyphenols, hydroxytyrosol (HT) and oleuropein aglycone (OLE), and their effects on ageing symptoms with special attention to PD. In order to avoid long-lasting, expensive, and ethically controversial experiments, the established invertebrate model organism Caenorhabditis elegans was used to test HT and OLE treatments. Interestingly, both polyphenols were able to increase the survival after heat stress, but only HT could prolong the lifespan in unstressed conditions. Furthermore, in aged worms, HT and OLE caused improvements of locomotive behavior and the attenuation of autofluorescence as a marker for ageing. In addition, by using three different C. elegans PD models, HT and OLE were shown i) to enhance locomotion in worms suffering from α-synuclein-expression in muscles or rotenone exposure, ii) to reduce α-synuclein accumulation in muscles cells, and iii) to prevent neurodegeneration in α-synuclein-containing dopaminergic neurons. Hormesis, antioxidative capacities and an activity-boost of the proteasome & phase II detoxifying enzymes are discussed as potential underlying causes for these beneficial effects. Further biological and medical trials are indicated to assess the full potential of HT and OLE and to uncover their mode of action.


Assuntos
Acetatos/uso terapêutico , Monoterpenos Ciclopentânicos/uso terapêutico , Neurônios Dopaminérgicos/metabolismo , Doença de Parkinson/prevenção & controle , Álcool Feniletílico/análogos & derivados , Piranos/uso terapêutico , alfa-Sinucleína , Acetatos/farmacologia , Animais , Animais Geneticamente Modificados , Caenorhabditis elegans/efeitos dos fármacos , Monoterpenos Ciclopentânicos/farmacologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/fisiologia , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Polifenóis/farmacologia , Piranos/farmacologia , Resultado do Tratamento
18.
Pestic Biochem Physiol ; 164: 122-129, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32284117

RESUMO

Imidacloprid (IMI) is a widely used neonicotinoid pesticide in the world, its environmental and human health risk has particularly attracted the attention of researchers. Caffeic acid phenethyl ester (CAPE), an active polyphenol of propolis, has many pharmacological activities including free radical scavenger, anti-inflammatory, and anti-oxidant. In this study, protective effect of CAPE against IMI induced liver injury in mice was performed. Administration of 1 and 2.5 mg/kg CAPE markedly prevented serum AST and ALT increase in 5 mg/kg IMI-induced mice. CAPE significantly downregulated liver NO generation and lipid peroxidation, and upregulated glutathione, catalase, superoxide dismutase and glutathione peroxidase in a dose-dependent manner in liver of IMI-induced mice. Endoplasmic reticulum stress represented by the swelling of endoplasmic reticulum was observed by transmission electron microscope in IMI group. Pretreatment of 2.5 mg/kg CAPE significantly attenuated the endoplasmic reticulum stress induced by IMI in liver. Western blot analysis illustrated that pretreatment of CAPE downregulated the upregulation of TNF-α and IFN-γ induced by IMI in liver of mice. Moreover, the increase of positive apoptotic hepatocytes further suggested apoptosis might be involved in IMI-induced hepatotoxicity. Pretreatment of 1 and 2.5 mg/kg CAPE significantly decreased positive apoptotic hepatocytes, suggested that CAPE prevented apoptosis in liver of IMI-induced mice. In conclusion, CAPE prevented liver injury in IMI-induced mice via attenuation of oxidative stress, endoplasmic reticulum stress, inflammation and apoptosis. Our findings may have broad biological and environmental implications for future research on the therapeutic strategy to prevent liver injury induced by pesticides.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Estresse do Retículo Endoplasmático , Animais , Antioxidantes , Apoptose , Ácidos Cafeicos , Humanos , Inflamação , Camundongos , Neonicotinoides , Nitrocompostos , Estresse Oxidativo , Álcool Feniletílico/análogos & derivados
19.
Sci Rep ; 10(1): 6361, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286485

RESUMO

Olive oil intake has been linked with a lower incidence of breast cancer. Hypoxic microenvironment in solid tumors, such as breast cancer, is known to play a crucial role in cancer progression and in the failure of anticancer treatments. HIF-1 is the foremost effector in hypoxic response, and given that hydroxytyrosol (HT) is one of the main bioactive compounds in olive oil, in this study we deepen into its modulatory role on HIF-1. Our results in MCF-7 breast cancer cells demonstrate that HT decreases HIF-1α protein, probably by downregulating oxidative stress and by inhibiting the PI3K/Akt/mTOR pathway. Strikingly, the expression of HIF-1 target genes does not show a parallel decrease. Particularly, adrenomedullin and vascular endothelial growth factor are up-regulated by high concentrations of HT even in HIF-1α silenced cells, pointing to HIF-1-independent mechanisms of regulation. In fact, we show, by in silico modelling and transcriptional analysis, that high doses of HT may act as an agonist of the aryl hydrocarbon receptor favoring the induction of these angiogenic genes. In conclusion, we suggest that the effect of HT in a hypoxic environment is largely affected by its concentration and involves both HIF-1 dependent and independent mechanisms.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Azeite de Oliva/farmacologia , Fenol/farmacologia , Álcool Feniletílico/análogos & derivados , Neoplasias da Mama/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Azeite de Oliva/química , Fenol/química , Álcool Feniletílico/metabolismo , Álcool Feniletílico/farmacologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética
20.
Nat Commun ; 11(1): 1515, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251291

RESUMO

Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, we design an efficient whole-cell catalyst of hydroxytyrosol in Escherichia coli by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of E. coli through structure-guided modeling and directed evolution. Next, we elucidate the structure of the Corynebacterium glutamicum VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.


Assuntos
Evolução Molecular Direcionada/métodos , Escherichia coli/enzimologia , Depuradores de Radicais Livres/metabolismo , Engenharia Metabólica , Álcool Feniletílico/análogos & derivados , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas Biossensoriais , Vias Biossintéticas/genética , Corynebacterium glutamicum/enzimologia , Corynebacterium glutamicum/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Estudos de Viabilidade , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Mutagênese Sítio-Dirigida , Mutação , Álcool Feniletílico/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tirosina/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Ácido Vanílico/metabolismo
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