RESUMEN
OBJECTIVES: This study aimed to evaluate silver nanoparticles (AgNPs) obtained by a 'green' route associated or not to tyrosol (TYR) against Streptococcus mutans and Candida albicans in planktonic and biofilms states. METHODS: AgNPs were obtained by a 'green' route using pomegranate extract. The minimum inhibitory concentration (MIC) against S. mutans and C. albicans was determined for AgNPs and TYR combined and alone, and fractional inhibitory concentration index (FICI) was calculated. Single biofilms of C. albicans and S. mutans were cultivated for 24 h and then treated with drugs alone or in combination for 24 h. RESULTS: AgNPs and TYR were effective against C. albicans and S. mutans considering planktonic cells alone and combined. The MIC values obtained for C. albicans was 312.5 µg/mL (AgNPs) and 50 mM (TYR) and for S. mutans was 78.1 µg/mL (AgNPs) and 90 mM (TYR). The combination of these antimicrobial agents was also effective against both microorganisms: 2.44 µg/mL/0.08 mM (AgNPs/TYR) for C. albicans and 39.05 µg/mL /1.25 mM (AgNPs/TYR) for S. mutans. However, synergism was observed only for C. albicans (FICI 0.008). When biofilm was evaluated, a reduction of 4.62 log10 was observed for S. mutans biofilm cells treated with AgNPs (p < 0.05, Tukey test). However, the addition of TYR to AgNPs did not improve their action against biofilm cells (p > 0.05). AgNPs combined with TYR demonstrated a synergistic effect against C. albicans biofilms. CONCLUSIONS: These findings suggest the potential use of AgNPs with or without TYR against C. albicans and S. mutans, important oral pathogens. CLINICAL SIGNIFICANCE: AgNPs obtained by a 'green' route combined or not with TYR can be an alternative to develop several types of oral antimicrobial therapies and biomaterials.
Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Alcohol Feniletílico , Alcohol Feniletílico/análogos & derivados , Plata/farmacología , Antiinfecciosos/farmacología , Alcohol Feniletílico/farmacología , Candida albicans , Biopelículas , Streptococcus mutansRESUMEN
Osteosarcoma is the most common type of bone cancer, and metastasis is widespread decreasing the survival rate. The search for new therapeutic strategies has increased for phytochemicals due to their potential as antioxidants and anticancer properties. Thus, we evaluated the caffeic acid phenethyl ester (CAPE) and caffeic acid's (CA) anticancer properties on UMR-106 murine osteosarcoma cells. The IC25 and IC50 were 1.3 and 2.7 µM for CAPE and 91.0 and 120.0 µM for CA, respectively. This study shows the potential anticancer properties of CAPE and highlights how a phenethyl ester component addition can improve the pharmacological potency in relation to its precursor CA. Our results showed that CAPE was more efficient and selective in reducing the viability of tumor cells compared to the control osteoblasts (MC3T3-E1) (p < 0.05). In addition, CAPE was 44-fold (IC25) and 70-fold (IC50) more cytotoxic than CA. CAPE also decreased ROS generation and cell migration. In summary, CAPE was more selective for tumor cells, preserving normal ones, suggesting its potential role as an anticancer drug.
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Antineoplásicos/farmacología , Neoplasias Óseas/tratamiento farmacológico , Ácidos Cafeicos/farmacología , Proliferación Celular/efectos de los fármacos , Osteosarcoma/tratamiento farmacológico , Alcohol Feniletílico/análogos & derivados , Animales , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ratones , Osteosarcoma/metabolismo , Osteosarcoma/patología , Alcohol Feniletílico/farmacologíaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the effects of caffeic acid phenethyl ester (CAPE) on osteoblast-like cell cultures (SAOS-2). METHODS: SAOS-2 were exposed to CAPE at 1 nM, 10 nM, 100 nM, 1 µM, and 10 µM. Non-exposed cultures were used as control. The following parameters were assayed: 1) cell viability at 1, 3, and 7 days; 2) alkaline phosphatase (ALP) activity at 5 and 10 days; 3) matrix mineralization at 14 days; and 4) Runt-related transcription factor 2 (RUNX2), ALP, osteopontin (SPP1), and osteocalcin (BGLAP) gene expression at 5 and 10 days. The data were analyzed by ANOVA two-way or Kruskal-Wallis (α = 5%). RESULTS: At day 1, cell viability was similar among all groups (p > 0.05). At days 3 and 7, cultures exposed to CAPE at 10 µM exhibited a significant reduction in cell viability compared with the others groups (p < 0.05). At day 5, ALP activity was similar among all experimental groups; at day 10, however, the stain intensity was higher in cultures exposed to CAPE at 100 nM and 10 nM in comparison with the other groups (p < 0.05). At days 5 and 10, RUNX2, ALP, SPP1, and BGLAP gene expression was greater in cultures exposed to CAPE in comparison with the control (p < 0.05). At day 14, matrix mineralization was similar in cultures exposed to CAPE at 1 nM and 10 nM (p > 0.05), but superior to those ones observed in the other experimental groups (p < 0.05). CONCLUSION: CAPE at low concentrations can positively module the osteogenesis in vitro.
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Ácidos Cafeicos/farmacología , Osteogénesis/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Matriz Ósea/efectos de los fármacos , Matriz Ósea/metabolismo , Calcificación Fisiológica/efectos de los fármacos , Calcificación Fisiológica/genética , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis/genética , Osteopontina/genética , Osteopontina/metabolismo , Alcohol Feniletílico/farmacologíaRESUMEN
Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.
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Ansiolíticos/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Própolis/farmacología , Animales , Brasil , Ácidos Cafeicos/farmacología , Humanos , Nueva Zelanda , Alcohol Feniletílico/análogos & derivados , Alcohol Feniletílico/farmacología , Fenilpropionatos/farmacologíaRESUMEN
2-phenylethanol (2-PE) is a higher aromatic alcohol with a rose-like aroma used in the cosmetic and food industries as a flavoring and displays potential for application as an antifungal. Biotechnological production of 2-PE from yeast is an interesting alternative due to the non-use of toxic compounds and the generation of few by-products. Kluyveromyces marxianus CCT 7735 is a thermotolerant strain capable of producing high 2-PE titers from L-Phenylalanine; however, like other yeast species, its growth has been strongly inhibited by this alcohol. Herein, we aimed to evaluate the effect of 2-PE on cell growth, cell viability, membrane permeability, glucose uptake, metabolism, and morphology in K. marxianus CCT 7735, as well as its adaptive responses. The stress condition was imposed after 4 h of cultivation by adding 3.0 g.L-1 of 2-PE in exponential growing cells. 2-PE stress impaired yeast growth, glucose uptake, fermentative metabolism, membrane permeability, and cell viability. Moreover, the stress condition provoked changes in both morphology and surface roughness. The reactive oxygen species (ROS) increased immediately on exposure to 2-PE. Changes in membrane fatty-acid composition, ergosterol content, exopolysaccharides production, and reduction of the ROS levels appear to be the result of adaptive responses in K. marxianus. Our results provided insights into a better understanding of the effects of 2-PE on K. marxianus and its adaptive responses.
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Adaptación Fisiológica , Polisacáridos Fúngicos/metabolismo , Kluyveromyces/efectos de los fármacos , Kluyveromyces/metabolismo , Alcohol Feniletílico/farmacología , Permeabilidad de la Membrana Celular , Ergosterol/metabolismo , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Lípidos de la Membrana/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés FisiológicoRESUMEN
SUMMARY: The aim of this study is to determine the potential therapeutic effects of CAPE in CP-induced nephrotoxicity in rats. Cisplatin (CP) is an antineoplastic chemotherapeutic used for treatment of many cancer types but its applications may induce nephrotoxicity. Caffeic acid phenethyl ester (CAPE) is an active component of propolis and it has several important physiological activities. Rats were divided into four groups: Control, CAPE (10 µmol/kg/i.p), CP (7 mg/kg/i.p), and CP+CAPE (7 mg/kg/i.p, CP and 10 µmol/kg/i.p, CAPE). After administrations, animals were sacrificed, and kidney tissues were extracted. Histopathological changes were evaluated and TNF-α and IL-6 immunostaining were performed. Moreover, tissue SOD, CAT and MDA levels were measured by ELISA assay to assessment of oxidative stress and lipid peroxidation. CP group showed histopathological deterioration compared to the Control group and CAPE treatment attenuated this damage. When compared with Control and CAPE group, an increase in TNF-α and IL-6 immunoreactivities and tissue MDA levels were observed in the CP group while a decrease in tissue SOD and CAT levels were detected. Furthermore, an improvement was observed in the CP+CAPE compared to the CP group. We suggest that CAPE can be used as a therapeutic agent to attenuate the toxic effects of cisplatin, thanks to its antioxidant and anti-inflammatory properties.
RESUMEN: El objetivo de este estudio fue determinar los posibles efectos terapéuticos de éster fenetílico del ácido cafeico (EFAC) en la nefrotoxicidad inducida por cisplatino (CP) en ratas. El CP es un quimioterapéutico antineoplásico utilizado para el tratamiento de muchos tipos de cáncer, sin embargo sus aplicaciones pueden inducir nefrotoxicidad. El EFAC es un componente activo del propóleo y tiene varias actividades fisiológicas importantes. Para el estudio las ratas se dividieron en cuatro grupos: Control, EFAC (10 µmol / kg / ip), CP (7 mg / kg / ip) y CP + EFAC (7 mg / kg / ip, CP y 10 µmol / kg / ip, EFAC). Después de las administraciones, se sacrificaron los animales y se extrajeron los tejidos renales. Se evaluaron los cambios histopatológicos y se realizó inmunotinción de TNF-α e IL-6. Además, los niveles tisulares de SOD, CAT y MDA se midieron mediante un ensayo ELISA para evaluar el estrés oxidativo y la peroxidación lipídica. El grupo CP mostró deterioro histopatológico en comparación con el grupo Control y el tratamiento con EFAC atenuó este daño. En comparación con el grupo de control y EFAC, se observó un aumento en las inmunorreactividades de TNF-α e IL-6 y los niveles de MDA en el tejido en el grupo de CP, mientras que se detectó una disminución en los niveles de SOD y CAT en los tejidos. Además, se observó una mejora en el CP + EFAC en comparación con el grupo CP. Sugerimos que EFAC puede utilizarse como agente terapéutico para atenuar los efectos tóxicos del cisplatino, gracias a sus propiedades antioxidantes y antiinflamatorias.
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Animales , Masculino , Ratas , Alcohol Feniletílico/análogos & derivados , Ácidos Cafeicos/farmacología , Cisplatino/toxicidad , Riñón/efectos de los fármacos , Alcohol Feniletílico/farmacología , Ensayo de Inmunoadsorción Enzimática , Inmunohistoquímica , Ratas Wistar , Estrés Oxidativo/efectos de los fármacos , Inflamación , Antineoplásicos/toxicidadRESUMEN
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 O2â-, whereas only 2-OH and 3-OH inhibited H2O2 and HOâ. The substrates exhibited a synergistic antioxidant effect when combined with commercial antioxidants. 2-OH showed antimicrobial activity against strains tested.
Asunto(s)
Aditivos Alimentarios/farmacología , Alcohol Feniletílico/análogos & derivados , Riboflavina/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Sinergismo Farmacológico , Peróxido de Hidrógeno/química , Radical Hidroxilo/química , Alcohol Feniletílico/química , Alcohol Feniletílico/farmacologíaRESUMEN
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.
Asunto(s)
Tejido Adiposo Blanco/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácido Eicosapentaenoico/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Obesidad , Alcohol Feniletílico/análogos & derivados , Tejido Adiposo Blanco/anomalías , Tejido Adiposo Blanco/patología , Animales , Masculino , Ratones , Obesidad/inducido químicamente , Obesidad/metabolismo , Obesidad/patología , Obesidad/prevención & control , Alcohol Feniletílico/farmacologíaRESUMEN
OBJECTIVE: Obesity-induced by high-fat diet (HFD) is associated with liver steatosis, oxidative stress and mitochondrial dysfunction, which can be eluded by the co-administration of the lipid metabolism modulator docosahexaenoic acid (DHA) and the antioxidant hydroxytyrosol (HT). METHODS: C57BL/6J mice fed a HFD were orally administered either with vehicle, DHA, HT or DHA+HT for 12 weeks. We measured parameters related to insulin resistance, serum lipid levels, liver fatty acid (FA) content and steatosis score, concomitantly with those associated with mitochondrial energy functions modulated by the transcriptional coactivator PGC-1a. RESULTS: HFD induced insulin resistance, liver steatosis with n-3 FA depletion, and loss of mitochondrial respiratory functions with diminished NAD+/NADH ratio and ATP levels compared with CD, with the parallel decrease in the expression of the components of the PGC-1α cascade, namely, PPAR-α, FGF21 and AMPK, effects that were not observed in mice subjected to DHA and HT co-administration. CONCLUSIONS: Data presented indicate that the combination of DHA and HT prevents the development of liver steatosis and the associated mitochondrial dysfunction induced by HFD, thus strengthening the significance of this protocol as a therapeutic strategy avoiding disease evolution into more irreversible forms characterised by the absence of adequate pharmacological therapy in human obesity.
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Ácidos Docosahexaenoicos/farmacología , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Obesidad/prevención & control , Alcohol Feniletílico/análogos & derivados , Animales , Dieta Alta en Grasa/efectos adversos , Ácidos Docosahexaenoicos/administración & dosificación , Humanos , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Alcohol Feniletílico/administración & dosificación , Alcohol Feniletílico/farmacología , Distribución AleatoriaRESUMEN
Parkinson's disease is considered to be due to an increase in the catabolism of dopamine by the action of monoamine oxidase (MAO) enzymes which leads to an increase in reactive oxygen species (ROS) and loss of dopaminergic neurons. Here, in a model of neurotoxicity inducible by 1-methyl-4-phenylpyridinium (MPP+), we tested the effect of hydroxytyrosol (HTy), a potent antioxidant, on generation of ROS. Five minutes after a single intravenous administration of 1.5 mg/Kg of Hty, Wistar rats received an intrastriatal micro-injection of 10 micrograms of MPP+ while control animals received saline solution. Six days later, all animals were treated with apomorphine (1 mg/Kg), subcutaneously and ipsilateral rotations were assessed within an hour. Then, the rats were sacrificed, striatal tissues were removed and their catecholamines and MAO-A and B activities were quantitated. Pretreatment with HTy significantly diminished the number of ipsilateral rotations. This recovery correlated with significant preservation of striatal dopamine and significant inhibition of of the MAO activity. These results are consistent with the inhibitory effect of HTy on the MAO isoforms and form a basis for the neuroprotective mechanism of this phenylpropanoid in MPP+ induced Parkinson's disease.
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Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/metabolismo , Alcohol Feniletílico/análogos & derivados , 1-Metil-4-fenilpiridinio/antagonistas & inhibidores , Animales , Antioxidantes/metabolismo , Catecolaminas , Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Monoaminooxidasa/farmacología , Enfermedad de Parkinson , Alcohol Feniletílico/farmacología , Isoformas de Proteínas/metabolismo , Ratas , Ratas WistarRESUMEN
Attenuation of high-fat diet (HFD)-induced liver steatosis is accomplished by different nutritional interventions. Considering that the n-3 PUFA docosahexaenoic acid (DHA) modulates lipid metabolism and the antioxidant hydroxytyrosol (HT) diminishes oxidative stress underlying fatty liver, it is hypothesized that HFD-induced steatosis is suppressed by DHA and HT co-administration. Male C57BL/6J mice were fed a control diet (CD; 10% fat, 20% protein, 70% carbohydrates) or a HFD (60% fat, 20% protein, 20% carbohydrates) for 12 weeks, without and with supplementation of DHA (50 mg/kg/day), HT (5 mg/kg/day) or both. The combined DHA + HT protocol fully prevented liver steatosis and the concomitant pro-inflammatory state induced by HFD, with suppression of lipogenic and oxidative stress signaling, recovery of fatty acid oxidation capacity and enhancement in resolvin availability affording higher inflammation resolution capability. Abrogation of HFD-induced hepatic steatosis by DHA and HT co-administration represents a crucial therapeutic strategy eluding disease progression into stages lacking efficacious handling at present time.
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Ácidos Docosahexaenoicos/farmacología , Hígado Graso/dietoterapia , Inflamación/dietoterapia , Alcohol Feniletílico/análogos & derivados , Animales , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Hígado Graso/etiología , Hígado Graso/genética , Hígado Graso/patología , Humanos , Inflamación/genética , Inflamación/patología , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Estrés Oxidativo/efectos de los fármacos , PPAR alfa/genética , Alcohol Feniletílico/farmacologíaRESUMEN
Peripheral sensory neuropathy (PSN) is a well-known side effect of cisplatin characterized by axonal damage. In the early stage of neurotoxicity, cisplatin affects proteins that modulate neurite outgrowth and neuroplasticity, without inducing mitochondrial damage or apoptosis. There are no preventive therapies for cisplatin-induced peripheral neuropathy; therefore, measures to improve axonal growth and connectivity would be beneficial. Caffeic acid phenethyl ester (CAPE) is a bioactive component of propolis with neurotrophic and neuroprotective activities. We have recently showed that CAPE protects against cisplatin-induced neurotoxicity by activating NGF high-affinity receptors (trkA) and inducing neuroplasticity. We have now assessed other potential early targets of cisplatin and additional mechanisms involved in the neuroprotection of CAPE. Cisplatin reduced axonal cytoskeletal proteins (F-actin and ß-III-tubulin) without inducing oxidative damage in PC12 cells. It also reduced energy-related proteins (AMPK α, p-AMPK α, and SIRT1) and glucose uptake. At this stage of neurotoxicity, glutamate excitotoxicity is not involved in the toxicity of cisplatin. CAPE attenuated the downregulation of the cytoskeleton and energy-related markers as well as SIRT1 and phosphorylated AMPK α. Moreover, the neuroprotective mechanism of CAPE also involves the activation of the neurotrophic signaling pathways MAPK/Erk and PI3k/Akt. The PI3K/Akt pathway is involved in the upregulation of SIRT1 induced by CAPE, but not in the upregulation of cytoskeletal proteins. Altogether, these findings suggest that the neuroprotective effect of CAPE against cisplatin-induced neurotoxicity involves both (a) a neurotrophic mechanism that mimics the mechanism triggered by the NGF itself and (b) a non-neurotrophic mechanism that upregulates the cytoskeletal proteins.
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Ácidos Cafeicos/farmacología , Cisplatino/toxicidad , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Alcohol Feniletílico/análogos & derivados , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Células COS , Diferenciación Celular/efectos de los fármacos , Chlorocebus aethiops , Proteínas del Citoesqueleto/metabolismo , Glucosa/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neuronas/metabolismo , Células PC12 , Alcohol Feniletílico/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/metabolismoRESUMEN
High-fat diet (HFD)-fed mice show obesity with development of liver steatosis and a proinflammatory state without establishing an inflammatory reaction. The aim of this work was to assess the hypothesis that eicosapentaenoic acid (EPA) plus hydroxytyrosol (HT) supplementation prevents the inflammatory reaction through enhancement in the hepatic resolvin content in HFD-fed mice. Male C57BL/6J mice were fed an HFD or a control diet and supplemented with EPA (50 mg/kg/day) and HT (5 mg/kg/day) or their respective vehicles for 12 weeks. Measurements include liver levels of EPA, DHA and palmitate (gas chromatography), liver resolvins and triglyceride (TG) and serum aspartate transaminase (AST) (specific kits) and hepatic and serum inflammatory markers (quantitative polymerase chain reaction and enzyme-linked immunosorbent assay). Compared to CD, HFD induced body weight gain, liver steatosis and TG accumulation, with up-regulation of proinflammatory markers in the absence of histological inflammation or serum AST changes; these results were accompanied by higher hepatic levels of resolvins RvE1, RvE2, RvD1 and RvD2, with decreases in EPA and DHA contents. EPA+HT supplementation in HFD feeding synergistically reduced the steatosis score over individual treatments and increased the hepatic levels of EPA, DHA and resolvins, with attenuation of proinflammatory markers. Lack of progression of HFD-induced proinflammatory state into overt inflammation is associated with resolvin up-regulation, which is further increased by EPA+HT supplementation eliciting steatosis attenuation. These findings point to the importance of combined protocols in hepatoprotection due to the involvement of cross-talk mechanisms, which increase effectiveness and diminish dosages, avoiding undesirable effects.
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Dieta Alta en Grasa/efectos adversos , Ácido Eicosapentaenoico/farmacología , Hepatitis/dietoterapia , Hígado/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Animales , Suplementos Dietéticos , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Ácidos Grasos/metabolismo , Hepatitis/etiología , Hepatitis/metabolismo , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Alcohol Feniletílico/farmacologíaRESUMEN
BACKGROUND: White adipose tissue (WAT) have a relevant metabolic and inflammatory function, in overweight or obesity conditions. In this regard, the WAT under over feeding nutrition present a significant increment in oxidative stress, pro-inflammatory status and depletion of n-3 long chain polyunsaturated fatty acid. Hydroxytyrosol (HT) is a polyphenol with important cytoprotective effects, and this molecule can modulate the gene expression, transcription factors and enzymatic activity. OBJECTIVE: Therefore, the purpose of this study was evaluate the anti-inflammatory, anti-oxidant and anti-lipogenic effects of HT supplementation mice and the molecular adaptations involved, on dysfunctional WAT from high-fat diet (HFD)-fed mice. METHODS AND RESULTS: Male C57BL/6 J mice received (i) control diet (10% fat); (ii) control diet + HT (daily doses of 5 mg kg body weight), (iii) HFD (60% fat); or (iv) HFD + HT for 12 weeks. HFD-fed mice exhibited: (i) WAT hypertrophy; (ii) oxidative stress and depletion of antioxidant defenses, (iii) increased lipogenesis and pro-inflammatory status, (iv) depletion of n-3 LCPUFA and (v) up-regulation of NF-κB and SREBP 1c with down-regulation Nrf2, and PPAR-γ. HT supplementation attenuated the metabolic impairment produced by HFD in WAT, attenuating increment of NF-κB and SREBP 1c, and increasing the activity of Nrf2 and PPAR-γ. CONCLUSION: Supplementation with HT improve the WAT dysfunction induced by HDF in mice through the modulation of transcription factors NF-κB, Nrf2, SREBP-1c and PPAR-γ as well as their target genes, involved in inflammation, antioxidant defenses and lipogenesis.
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Tejido Adiposo Blanco/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , PPAR gamma/metabolismo , Alcohol Feniletílico/análogos & derivados , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Tejido Adiposo Blanco/efectos de los fármacos , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Dieta Alta en Grasa/tendencias , Masculino , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/metabolismo , Ratones , Ratones Endogámicos C57BL , FN-kappa B/antagonistas & inhibidores , Alcohol Feniletílico/farmacología , Alcohol Feniletílico/uso terapéutico , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/antagonistas & inhibidores , Factores de Transcripción/metabolismoRESUMEN
Antioxidant compounds have the ability to scavenge the reactive oxygen species in an attempt to minimise damage in seeds during the germination. This study aimed to evaluate the physiological and metabolic process of two well-established antioxidant compounds: kojic acid and hydroxyphenyl ethanol (tyrosol), at increasing concentrations, on wheat seeds. The use of different concentrations of tyrosol or kojic acid not showed any interference on seed germination rate. However, we observed isolated effect of antioxidants and their concentrations to: germination speed index, shoot length and electrolyte leakage; and significant interaction between the factors to: seedling total length, seedling fresh matter and α-amylase activity. Our results suggest that the use of antioxidant molecules can be applied on seed treatments for protection against damage oxidative stress and improve seed metabolism.
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Hongos/química , Germinación/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Pironas/farmacología , Triticum/efectos de los fármacos , Antioxidantes/farmacología , Membrana Celular/efectos de los fármacos , Endófitos/química , Estrés Oxidativo , Alcohol Feniletílico/farmacología , Especies Reactivas de Oxígeno/metabolismo , Plantones/efectos de los fármacos , Semillas/efectos de los fármacosRESUMEN
Cisplatin is a highly effective chemotherapeutic drug that is toxic to the peripheral nervous system. Findings suggest that axons are early targets of the neurotoxicity of cisplatin. Although many compounds have been reported as neuroprotective, there is no effective treatment against the neurotoxicity of cisplatin. Caffeic acid phenethyl ester (CAPE) is a propolis component with neuroprotective potential mainly attributed to antioxidant and anti-inflammatory mechanisms. We have recently demonstrated the neurotrophic potential of CAPE in a cellular model of neurotoxicity related to Parkinson's disease. Now, we have assessed the neurotrophic and neuroprotective effects of CAPE against cisplatin-induced neurotoxicity in PC12 cells. CAPE (10 µM) attenuated the inhibition of neuritogenesis and the downregulation of markers of neuroplasticity (GAP-43, synapsin I, synaptophysin, and 200-kD neurofilament) induced by cisplatin (5 µM). This concentration of cisplatin does not affect cell viability, and it was used in order to assess the early neurotoxic events triggered by cisplatin. When a lethal dose of cisplatin was used (IC50 = 32 µM), CAPE (10 µM) increased cell viability. The neurotrophic effect of CAPE is not dependent on NGF nor is it additive to the effect of NGF, but it might involve the activation of the NGF-high-affinity receptors (trkA). The involvement of other neurotrophin receptors such as trkB and trkC is unlikely. This is the first study to demonstrate the protective potential of CAPE against the neurotoxicity of cisplatin and to suggest the involvement of trkA receptors in the neuroprotective mechanism of CAPE. Based on these findings, the beneficial effect of CAPE on cisplatin-induced peripheral neuropathy should be further investigated.
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Ácidos Cafeicos/farmacología , Cisplatino/farmacología , Factor de Crecimiento Nervioso/metabolismo , Fármacos Neuroprotectores/farmacología , Neurotoxinas/farmacología , Alcohol Feniletílico/análogos & derivados , Transducción de Señal/efectos de los fármacos , Análisis de Varianza , Animales , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Proteína GAP-43/metabolismo , Neuroblastoma/patología , Proteínas de Neurofilamentos/metabolismo , Proyección Neuronal/efectos de los fármacos , Células PC12/efectos de los fármacos , Alcohol Feniletílico/farmacología , Ratas , Sinapsinas/metabolismo , Sinaptofisina/metabolismoRESUMEN
PURPOSE: To assess the effect of tyrosol on the production of hydrolytic enzymes (by Candida biofilm cells) and acid (by Streptococcus mutans biofilms), as well as to quantify single and mixed biofilms of these species formed on acrylic resin (AR) and hydroxyapatite (HA). METHODS: Candida and S. mutans biofilms were formed on AR and HA in the presence of tyrosol during 48 hours. Next, acid proteinase, phospholipase and hemolytic activities of Candida biofilm cells were determined, while acid production by S. mutans biofilms was assessed by pH determination. The effect of tyrosol on mature biofilms (96 hours) was evaluated through quantification of total biomass, metabolic activity, number of colony-forming units and composition of biofilms' extracellular matrix. Data were analyzed by one- and two-way ANOVA, followed by Tukey's and Holm-Sidak's tests (α = 0.05). RESULTS: Treatments with tyrosol were not able to significantly reduce hydrolytic enzymes and acid production by Candida and S. mutans. Tyrosol only significantly reduced the metabolic activity of single biofilms of Candida species. CLINICAL SIGNIFICANCE: Tyrosol on its own had a limited efficacy against single and mixed-species oral biofilms. Its use as an alternative antimicrobial for topical therapies still demands more investigation.
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Antioxidantes/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida glabrata/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Streptococcus mutans/efectos de los fármacos , Resinas Acrílicas/química , Candida albicans/enzimología , Candida glabrata/enzimología , Adhesión Celular/efectos de los fármacos , Durapatita/química , Concentración de Iones de Hidrógeno , Alcohol Feniletílico/farmacología , Streptococcus mutans/enzimología , Propiedades de SuperficieRESUMEN
AIM: This study examined the antifungal activity of the combination of tyrosol and farnesol against Candida albicans and Candida glabrata in the planktonic state or forming biofilms. METHODS AND RESULTS: The effect of drug association against Candida planktonic cells was assessed by the fractional inhibitory concentration index. Mono- and dual-species biofilms were developed during 24 h and then treated with the compounds for 3 days, with two daily treatments of 1 min each. After, the total biomass, metabolic activity and the number of cultivable cells were quantified. Planktonic cells of the two species showed a similar susceptibility to the drug combination, however, a synergistic effect was only verified for C. glabrata. Regarding biofilm susceptibility, significant reductions in C. glabrata biomass, metabolism of C. albicans and mixed biofilms, and cultivable cells of single biofilms were verified for the drug combination, indicating an additive effect. For all other experiments, the effects were classified as indifferent. CONCLUSION: The combined use of tyrosol and farnesol was advantageous for some of the analysed parameters against Candida species. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings may contribute to the development of oral care products containing tyrosol and farnesol to combat oral infections caused by Candida species.
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Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Candida albicans/efectos de los fármacos , Candida glabrata/efectos de los fármacos , Farnesol/farmacología , Alcohol Feniletílico/análogos & derivados , Plancton/efectos de los fármacos , Candida albicans/genética , Candida albicans/fisiología , Candida glabrata/genética , Candida glabrata/fisiología , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Alcohol Feniletílico/farmacología , Plancton/genética , Plancton/fisiologíaRESUMEN
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used medications in inflammatory illnesses. However, the gastrointestinal bleeding and toxicity associated with NSAIDs long term use prompted the quest towards investigations for new anti-inflammatory agents. Natural and natural-derived molecules proved its anti-inflammatory efficacy in vitro as well as in vivo. Given this background, the scope of this research involves structural changes of the natural polyphenol (tyrosol) generating two new salicylate derivatives and testing their biological properties, focusing on anti-inflammatory effects assessed in vitro and in vivo assays. The first molecular modification was the introduction of a carboxylic acid group adjacent to the phenol group present in this compound, which creates a new salicylate-like tyrosol. In addition, the acetylation of phenol group in this molecule produced an acetylsalicylate derivative, which may be regarded as aspirin-like natural polyphenol. Interestingly, tyrosol and its novel derivatives attenuated the edema in acute inflammatory response on carrageenan- induced local inflammation in mice. In addition, our results demonstrated that tyrosol and its novel derivatives were able to reduce the chemotaxis of neutrophil assessed in vitro model by chemo attractant (fMLP). Furthermore, only derivative 2 was able to reduce this effect in the acute inflammatory model. In (DPPH)- scavenging activity, tyrosol derivatives demonstrated a minor antioxidant activity, which may suggest that radical scavenging is not a major pathway involved in the anti-inflammatory effects of these derivatives. Salicylate-like tyrosol derivatives are of particular interest for future studies.
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Antiinflamatorios no Esteroideos/farmacología , Edema/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Alcohol Feniletílico/análogos & derivados , Salicilatos/síntesis química , Salicilatos/farmacología , Animales , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/química , Carragenina , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Edema/inducido químicamente , Inflamación/inducido químicamente , Masculino , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Alcohol Feniletílico/síntesis química , Alcohol Feniletílico/química , Alcohol Feniletílico/farmacología , Salicilatos/química , Relación Estructura-ActividadRESUMEN
Hydroxytyrosol (HT) ((3,4-Dihydroxyphenyl)ethanol) is a polyphenol mainly present in extra virgin olive oil (EVOO) but also in red wine. It has a potent antioxidant effect related to hydrogen donation, and the ability to improve radical stability. The phenolic content of olive oil varies between 100 and 600 mg/kg, due to multiple factors (place of cultivation, climate, variety of the olive and level of ripening at the time of harvest), with HT and its derivatives providing half of that content. When consumed, EVOO's phenolic compounds are hydrolyzed in the stomach and intestine, increasing levels of free HT which is then absorbed in the small intestine, forming phase II metabolites. It has been demonstrated that HT consumption is safe even at high doses, and that is not genotoxic or mutagenic in vitro. The beneficial effects of HT have been studied in humans, as well as cellular and animal models, mostly in relation to consumption of EVOO. Many properties, besides its antioxidant capacity, have been attributed to this polyphenol. The aim of this review was to assess the main properties of HT for human health with emphasis on those related to the possible prevention and/or treatment of non-communicable diseases.