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1.
Sci Rep ; 14(1): 15666, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977845

RESUMO

Inter-cellular signaling, referred to as quorum sensing (QS), regulates the production of virulence factors in numerous gram-negative bacteria, such as the human pathogens Pseudomonas aeruginosa and Chromobacterium violaceum. QS inhibition may provide an opportunity for the treatment of bacterial infections. This represents the initial study to examine the antibiofilm and antivirulence capabilities of rose absolute and its primary component, phenylethyl alcohol. QS inhibition was assessed by examining extracellular exopolysaccharide synthesis, biofilm development, and swarming motility in P. aeruginosa PAO1, along with violacein production in C. violaceum ATCC 12472. Molecular docking analysis was conducted to explore the mechanism by which PEA inhibits QS. Our results indicate that rose absolute and PEA caused decrease in EPS production (60.5-33.5%), swarming motility (94.7-64.5%), and biofilm formation (98.53-55.5%) in the human pathogen P. aeruginosa PAO1. Violacein production decreased by 98.1% and 62.5% with an absolute (0.5 v/v %) and PEA (2 mM). Moreover, the molecular docking analysis revealed a promising competitive interaction between PEA and AHLs. Consequently, this study offers valuable insights into the potential of rose absolute and PEA as inhibitors of QS in P. aeruginosa and C. violaceum.


Assuntos
Biofilmes , Chromobacterium , Simulação de Acoplamento Molecular , Álcool Feniletílico , Pseudomonas aeruginosa , Percepção de Quorum , Percepção de Quorum/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Chromobacterium/efeitos dos fármacos , Chromobacterium/fisiologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Álcool Feniletílico/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Indóis/farmacologia , Indóis/metabolismo
2.
Nat Commun ; 15(1): 5683, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971825

RESUMO

Bacteria within mature biofilms are highly resistant to antibiotics than planktonic cells. Oxygen limitation contributes to antibiotic resistance in mature biofilms. Nitric oxide (NO) induces biofilm dispersal; however, low NO levels stimulate biofilm formation, an underexplored process. Here, we introduce a mechanism of anaerobic biofilm formation by investigating the antibiofilm activity of tyrosol, a component in wine. Tyrosol inhibits E. coli and Pseudomonas aeruginosa biofilm formation by enhancing NO production. YbfA is identified as a target of tyrosol and its downstream targets are sequentially determined. YbfA activates YfeR, which then suppresses the anaerobic regulator FNR. This suppression leads to decreased NO production, elevated bis-(3'-5')-cyclic dimeric GMP levels, and finally stimulates anaerobic biofilm formation in the mature stage. Blocking YbfA with tyrosol treatment renders biofilm cells as susceptible to antibiotics as planktonic cells. Thus, this study presents YbfA as a promising antibiofilm target to address antibiotic resistance posed by biofilm-forming bacteria, with tyrosol acting as an inhibitor.


Assuntos
Antibacterianos , Biofilmes , Escherichia coli , Óxido Nítrico , Álcool Feniletílico , Pseudomonas aeruginosa , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Óxido Nítrico/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/antagonistas & inibidores , Anaerobiose/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , GMP Cíclico/metabolismo , GMP Cíclico/análogos & derivados , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/antagonistas & inibidores
3.
J Agric Food Chem ; 72(27): 15293-15300, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38940657

RESUMO

Hydroxytyrosol, a naturally occurring compound with antioxidant and antiviral activity, is widely applied in the cosmetic, food, and nutraceutical industries. The development of a biocatalytic approach for producing hydroxytyrosol from simple and readily accessible substrates remains a challenge. Here, we designed and implemented an effective biocatalytic cascade to obtain hydroxytyrosol from 3,4-dihydroxybenzaldehyde and l-threonine via a four-step enzymatic cascade composed of seven enzymes. To prevent cross-reactions and protein expression burden caused by multiple enzymes expressed in a single cell, the designed enzymatic cascade was divided into two modules and catalyzed in a stepwise manner. The first module (FM) assisted the assembly of 3,4-dihydroxybenzaldehyde and l-threonine into (2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid, and the second module (SM) entailed converting (2S,3R)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid into hydroxytyrosol. Each module was cloned into Escherichia coli BL21 (DE3) and engineered in parallel by fine-tuning enzyme expression, resulting in two engineered whole-cell catalyst modules, BL21(FM01) and BL21(SM13), capable of converting 30 mM 3,4-dihydroxybenzaldehyde to 28.7 mM hydroxytyrosol with a high space-time yield (0.88 g/L/h). To summarize, the current study proposes a simple and effective approach for biosynthesizing hydroxytyrosol from low-cost substrates and thus has great potential for industrial applications.


Assuntos
Biocatálise , Escherichia coli , Álcool Feniletílico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/química , Álcool Feniletílico/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Benzaldeídos/química , Benzaldeídos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química
4.
Int J Food Microbiol ; 421: 110788, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-38905810

RESUMO

During alcoholic fermentation, Saccharomyces cerevisiae synthesizes different compounds, which are crucial for product quality: volatile compounds with sensory impact, and bioactive compounds such as melatonin (MEL) and hydroxytyrosol (HT), linked to health benefits. As many of these compounds are related with yeast's nitrogen metabolism, their production have been studied in four different commercial strains with different nitrogen requirement (Red Fruit, Uvaferm VRB, Lalvin Rhone 2323 and Lalvin QA23) being, Uvaferm UVR the higher nitrogen demander strain. All strains produced the secondary metabolites, notably Uvaferm UVR produced the highest HT concentration, despite its low growth. Uvaferm UVR emerged also as a significant producer of MEL, indicating a potential role in fermentation related stress. Moreover, Uvaferm UVR shows the highest total concentrations of volatile compounds. Multivariate analysis revealed distinct clustering based on nitrogen requirements of the strains, highlighting the strain-dependent metabolic responses.


Assuntos
Fermentação , Melatonina , Nitrogênio , Álcool Feniletílico , Saccharomyces cerevisiae , Vinho , Saccharomyces cerevisiae/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/metabolismo , Vinho/microbiologia , Vinho/análise , Nitrogênio/metabolismo , Melatonina/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Metabolismo Secundário , Odorantes/análise
5.
Sci Rep ; 14(1): 14546, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914695

RESUMO

Caffeic acid phenethyl ester (CAPE) and its derivatives exhibit considerable effects against hepatocellular carcinoma (HCC), with unquestioned safety. Here we investigated CAPE derivative 1' (CAPE 1') monotherapy to HCC, compared with sorafenib. HCC Bel-7402 cells were treated with CAPE 1', the IC50 was detected using CCK-8 analysis, and acute toxicity testing (5 g/kg) was performed to evaluate safety. In vivo, tumor growth after CAPE 1' treatment was evaluated using an subcutaneous tumor xenograft model. Five groups were examined, with group 1 given vehicle solution, groups 2, 3, and 4 given CAPE 1' (20, 50, and 100 mg/kg/day, respectively), and group 5 given sorafenib (30 mg/kg/day). Tumor volume growth and tumor volume-to-weight ratio were calculated and statistically analyzed. An estimated IC50 was 5.6 µM. Acute toxicity tests revealed no animal death or visible adverse effects with dosage up to 5 g/kg. Compared to negative controls, CAPE 1' treatment led to significantly slower increases of tumor volume and tumor volume-to-weight. CAPE 1' and sorafenib exerted similar inhibitory effects on HCC tumors. CAPE 1' was non-inferior to sorafenib for HCC treatment, both in vitro and in vivo. It has great potential as a promising drug for HCC, based on effectiveness and safety profile.


Assuntos
Antineoplásicos , Ácidos Cafeicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Álcool Feniletílico , Sorafenibe , Ensaios Antitumorais Modelo de Xenoenxerto , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Animais , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Camundongos Endogâmicos BALB C , Masculino
6.
Sci Rep ; 14(1): 14582, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918455

RESUMO

Volatile organic compounds (VOCs) are metabolites pivotal in determining the aroma of various products. A well-known VOC producer of industrial importance is Saccharomyces cerevisiae, partially responsible for flavor of beers and wines. We identified VOCs in beers produced by yeast strains characterized by improved aroma obtained in UV-induced mutagenesis. We observed significant increase in concentration of compounds in strains: 1214uv16 (2-phenylethyl acetate, 2- phenylethanol), 1214uv31 (2-ethyl henxan-1-ol), 1214uv33 (ethyl decanoate, caryophyllene). We observed decrease in production of 2-phenyethyl acetate in strain 1214uv33. Analysis of intracellular metabolites based on 1H NMR revealed that intracellular phenylalanine concentration was not changed in strains producing more phenylalanine related VOCs (1214uv16 and 1214uv33), so regulation of this pathway seems to be more sophisticated than is currently assumed. Metabolome analysis surprisingly showed the presence of 3-hydroxyisobutyrate, a product of valine degradation, which is considered to be absent in S. cerevisiae. Our results show that our knowledge of yeast metabolism including VOC production has gaps regarding synthesis pathways for individual metabolites and regulation mechanisms. Detailed analysis of 1214uv16 and 1214uv33 may enhance our knowledge of the regulatory mechanisms of VOC synthesis in yeast, and analysis of strain 1214uv31 may reveal the pathway of 2-ethyl henxan-1-ol biosynthesis.


Assuntos
Cerveja , Metaboloma , Mutação , Saccharomyces cerevisiae , Compostos Orgânicos Voláteis , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Cerveja/análise , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Odorantes/análise , Álcool Feniletílico/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/análise , Fermentação , Fenilalanina/metabolismo , Fenilalanina/análise , Metabolômica/métodos , Acetatos
7.
Sci Rep ; 14(1): 14624, 2024 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918541

RESUMO

Colon cancer ranks as the third most prevalent form of cancer globally, with chemotherapy remaining the primary treatment modality. To mitigate drug resistance and minimize adverse effects associated with chemotherapy, selection of appropriate adjuvants assumes paramount importance. Caffeic acid phenethyl ester (CAPE), a naturally occurring compound derived from propolis, exhibits a diverse array of biological activities. We observed that the addition of CAPE significantly augmented the drug sensitivity of colon cancer cells to oxaliplatin. In SW480 and HCT116 cells, oxaliplatin combined with 10 µM CAPE reduced the IC50 of oxaliplatin from 14.24 ± 1.03 and 84.16 ± 3.02 µM to 2.11 ± 0.15 and 3.92 ± 0.17 µM, respectively. We then used proteomics to detect differentially expressed proteins in CAPE-treated SW480 cells and found that the main proteins showing changes in expression after CAPE treatment were p62 (SQSTM1) and LC3B (MAP1LC3B). Gene ontology analysis revealed that CAPE exerted antitumor and chemotherapy-sensitization effects through the autophagy pathway. We subsequently verified the differentially expressed proteins using immunoblotting. Simultaneously, the autophagy inhibitor bafilomycin A1 and the mCherry-EGFP-LC3 reporter gene were used as controls to detect the effect of CAPE on autophagy levels. Collectively, the results indicate that CAPE may exert antitumor and chemotherapy-sensitizing effects by inhibiting autophagy, offering novel insights for the development of potential chemosensitizing agents.


Assuntos
Autofagia , Ácidos Cafeicos , Neoplasias do Colo , Oxaliplatina , Álcool Feniletílico , Humanos , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Autofagia/efeitos dos fármacos , Oxaliplatina/farmacologia , Ácidos Cafeicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Células HCT116 , Sinergismo Farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos
8.
Food Chem Toxicol ; 190: 114818, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38880467

RESUMO

Testicular heat stress disrupts spermiogenesis and damages testicular tissue. The study aims to assess 3,4-dihydroxyphenylglycol (DHPG) and hydroxytyrosol (HT) from olive oil as antioxidants to reduce heat-induced testicular damage. Seven groups of 35 male rats were used. Group I got normal saline. Group 2 had HS (43 °C for 20 min/day) and normal saline for 60 days. Groups 3-7 had HS and DHPG/HT doses (0.5 mg/kg DHPG, 1 mg/kg DHPG, 5 mg/kg HT, 0.5 mg/kg DHPG + 5 mg/kg HT, and 1 mg/kg DHPG + 5 mg/kg HT). The evaluation included tests on testicular tissue, sperm quality, oxidative status, gene activity, and fertility after 60 days. After DHPG and HT treatment, sperm motility, viability, and plasma membrane functionality, as well as levels of total antioxidant capacity (TAC), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), and Bcl-2 gene expression, and in vivo fertility indexes increased. Meanwhile, abnormal morphology and DNA damage decreased, along with levels of glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA), and Bax, caspase-3, and caspase-9 gene expression, compared to the HS group. The study found that DHPG and HT have a more substantial synergistic effect when used together, improving reproductive health.


Assuntos
Metoxi-Hidroxifenilglicol , Álcool Feniletílico , Motilidade dos Espermatozoides , Testículo , Animais , Masculino , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Ratos , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/farmacologia , Testículo/efeitos dos fármacos , Testículo/metabolismo , Motilidade dos Espermatozoides/efeitos dos fármacos , Antioxidantes/farmacologia , Espermatozoides/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Sinergismo Farmacológico , Ratos Wistar , Reprodução/efeitos dos fármacos , Resposta ao Choque Térmico/efeitos dos fármacos , Superóxido Dismutase/metabolismo
9.
Int J Mol Sci ; 25(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38891778

RESUMO

Infants and young animals often suffer from intestinal damage caused by oxidative stress, which may adversely affect their overall health. Hydroxytyrosol, a plant polyphenol, has shown potential in decreasing intestinal oxidative stress, but its application and mechanism of action in infants and young animals are still inadequately documented. This study selected piglets as a model to investigate the alleviating effects of hydroxytyrosol on intestinal oxidative stress induced by diquat and its potential mechanism. Hydroxytyrosol improved intestinal morphology, characterized by higher villus height and villus height/crypt depth. Meanwhile, hydroxytyrosol led to higher expression of Occludin, MUC2, Nrf2, and its downstream genes, and lower expression of cytokines IL-1ß, IL-6, and TNF-α. Both oxidative stress and hydroxytyrosol resulted in a higher abundance of Clostridium_sensu_stricto_1, and a lower abundance of Lactobacillus and Streptococcus, without a significant effect on short-chain fatty acids levels. Oxidative stress also led to disorders in bile acid (BA) metabolism, such as the lower levels of primary BAs, hyocholic acid, hyodeoxycholic acid, and tauroursodeoxycholic acid, which were partially restored by hydroxytyrosol. Correlation analysis revealed a positive correlation between these BA levels and the expression of Nrf2 and its downstream genes. Collectively, hydroxytyrosol may reduce oxidative stress-induced intestinal damage by regulating BA metabolism.


Assuntos
Ácidos e Sais Biliares , Mucosa Intestinal , Estresse Oxidativo , Álcool Feniletílico , Animais , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Suínos , Ácidos e Sais Biliares/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética
10.
Sheng Wu Gong Cheng Xue Bao ; 40(6): 1694-1710, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38914486

RESUMO

2-phenylethanol (2-PE), an aromatic alcohol with a rose fragrance, is the second most widely used flavoring substance in the world. It is widely used in the cosmetic, food, and pharmaceutical industries. This paper introduces the chemical synthesis methods of 2-PE and the synthetic pathways in plants and microorganisms, summarizes the strategies to improve the microbial synthesis of 2-PE, reviews the research progress in de novo synthesis of 2-PE in microorganisms, and makes an outlook on the research prospects, aiming to provide a theoretical basis for the industrial production of 2-PE.


Assuntos
Álcool Feniletílico , Álcool Feniletílico/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/síntese química , Microbiologia Industrial , Aromatizantes/síntese química , Aromatizantes/metabolismo , Bactérias/metabolismo , Plantas/metabolismo
11.
Molecules ; 29(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38893586

RESUMO

Hemerocallis L. possesses abundant germplasm resources and holds significant value in terms of ornamental, edible, and medicinal aspects. However, the quality characteristics vary significantly depending on different varieties. Selection of a high-quality variety with a characteristic aroma can increase the economic value of Hemerocallis flowers. The analytic hierarchy process (AHP) is an effective decision-making method for comparing and evaluating multiple characteristic dimensions. By applying AHP, the aromatic character of 60 varieties of Hemerocallis flowers were analyzed and evaluated in the present study. Headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) was employed to identify volatile components in Hemerocallis flowers. Thirteen volatile components were found to contribute to the aroma of Hemerocallis flowers, which helps in assessing their potential applications in essential oil, aromatherapy, and medical treatment. These components include 2-phenylethanol, geraniol, linalool, nonanal, decanal, (E)-ß-ocimene, α-farnesene, indole, nerolidol, 3-furanmethanol, 3-carene, benzaldehyde and benzenemethanol. The varieties with better aromatic potential can be selected from a large amount of data using an AHP model. This study provides a comprehensive understanding of the characteristics of the aroma components in Hemerocallis flowers, offers guidance for breeding, and enhances the economic value of Hemerocallis flowers.


Assuntos
Flores , Cromatografia Gasosa-Espectrometria de Massas , Microextração em Fase Sólida , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Microextração em Fase Sólida/métodos , Flores/química , Odorantes/análise , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/análise , Óleos Voláteis/química , Óleos Voláteis/análise , Sesquiterpenos/análise , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/análise , Álcool Feniletílico/química , Alcenos , Indóis
12.
Reprod Domest Anim ; 59(6): e14588, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38822558

RESUMO

Semen cryopreservation is one of the most important reproduction techniques in the livestock and poultry industry. Cryopreservation induces cold stress, generating reactive oxygen species (ROS) and oxidative stress causing structural and biochemical damages in sperm. In this study, we evaluated the effects of the hydroxytyrosol (HT), as an antioxidant, at the concentrations of 0, 25, 50, and 100 µg/mL on post-thaw semen quality metrics in rooster. Semen samples were collected twice a week from 10 roosters (29 weeks), processed and frozen according to experimental groups. Different quality parameters, including total motility, progressive motility, viability, morphology, membrane integrity, and malondialdehyde were measured after thawing. Results showed that 25 and 50 µg/mL of HT produced the highest percentage of total motility (51.01 ± 2.19 and 50.15 ± 2.19, respectively) and progressive motility (35.74 ± 1.34 and 35.15 ± 1.34, respectively), membrane integrity (48.00 ± 2.18 and 46.75 ± 2.18, respectively) as well as viability (53.00 ± 2.17 and 52.50 ± 2.17, respectively) compared with the other groups (p < .05). The group with 25 µg/mL of HT showed the lowest significant (p < .05) MDA concentration (1.81 ± 0.25). Our results showed that the effect of HT was not dose-dependent and optimum concentration of HT could improve functional parameters of rooster sperm after freezing-thawing. These findings suggest that HT may have protective effects on the rooster sperm during the freezing-thawing process.


Assuntos
Antioxidantes , Galinhas , Criopreservação , Álcool Feniletílico , Preservação do Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Animais , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Masculino , Criopreservação/veterinária , Criopreservação/métodos , Preservação do Sêmen/veterinária , Preservação do Sêmen/métodos , Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Antioxidantes/farmacologia , Análise do Sêmen/veterinária , Crioprotetores/farmacologia , Malondialdeído/análise
13.
Food Funct ; 15(13): 7214-7223, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38817211

RESUMO

Parkinson's disease is the neurodegenerative motor disorder with the highest incidence worldwide. Among other factors, Parkinson's disease is caused by the accumulation of α-synuclein aggregates in a patient's brain. In this work, five molecules present in the diet are proposed as possible nutraceuticals to prevent and/or reduce the formation of α-synuclein oligomers that lead to Parkinson's disease. The olive oil polyphenols tyrosol, hydroxytyrosol (HT), hydroxytyrosol acetate (HTA) and dihydroxyphenyl acetic acid (DOPAC) besides vitamin C were tested using a cellular model of α-synuclein aggregation and a Caenorhabditis elegans Parkinson's disease animal model. Levodopa was included in the assays as the main drug prescribed to treat the disease as well as dopamine, its direct metabolite. HTA and DOPAC completely hindered α-synuclein aggregation in vitro, while dopamine reduced the aggregation by 28.7%. The Parallel Artificial Membrane Permeability Assay (PAMPA) showed that HTA had the highest permeability through brain lipids among the compounds tested. Furthermore, the C. elegans Parkinson's disease model made it possible to assess the chosen compounds in vivo. The more effective substances in vivo were DOPAC and HTA which reduced the αS aggregation inside the animals by 79.2% and 76.2%, respectively. Moreover, dopamine also reduced the aggregates by 67.4% in the in vivo experiment. Thus, the results reveal the potential of olive oil tyrosols as nutraceuticals against α-synuclein aggregation.


Assuntos
Caenorhabditis elegans , Modelos Animais de Doenças , Azeite de Oliva , Doença de Parkinson , Álcool Feniletílico , alfa-Sinucleína , Animais , Caenorhabditis elegans/efeitos dos fármacos , alfa-Sinucleína/metabolismo , Azeite de Oliva/química , Azeite de Oliva/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Álcool Feniletílico/química , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Humanos , Agregados Proteicos/efeitos dos fármacos , Suplementos Nutricionais
14.
Ren Fail ; 46(1): 2350235, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38721924

RESUMO

Increasing evidence suggests that peritoneal fibrosis induced by peritoneal dialysis (PD) is linked to oxidative stress. However, there are currently no effective interventions for peritoneal fibrosis. In the present study, we explored whether adding caffeic acid phenethyl ester (CAPE) to peritoneal dialysis fluid (PDF) improved peritoneal fibrosis caused by PD and explored the molecular mechanism. We established a peritoneal fibrosis model in Sprague-Dawley rats through intraperitoneal injection of PDF and lipopolysaccharide (LPS). Rats in the PD group showed increased peritoneal thickness, submesothelial collagen deposition, and the expression of TGFß1 and α-SMA. Adding CAPE to PDF significantly inhibited PD-induced submesothelial thickening, reduced TGFß1 and α-SMA expression, alleviated peritoneal fibrosis, and improved the peritoneal ultrafiltration function. In vitro, peritoneal mesothelial cells (PMCs) treated with PDF showed inhibition of the AMPK/SIRT1 pathway, mitochondrial membrane potential depolarization, overproduction of mitochondrial reactive oxygen species (ROS), decreased ATP synthesis, and induction of mesothelial-mesenchymal transition (MMT). CAPE activated the AMPK/SIRT1 pathway, thereby inhibiting mitochondrial membrane potential depolarization, reducing mitochondrial ROS generation, and maintaining ATP synthesis. However, the beneficial effects of CAPE were counteracted by an AMPK inhibitor and siSIRT1. Our results suggest that CAPE maintains mitochondrial homeostasis by upregulating the AMPK/SIRT1 pathway, which alleviates oxidative stress and MMT, thereby mitigating the damage to the peritoneal structure and function caused by PD. These findings suggest that adding CAPE to PDF may prevent and treat peritoneal fibrosis.


Assuntos
Proteínas Quinases Ativadas por AMP , Ácidos Cafeicos , Diálise Peritoneal , Fibrose Peritoneal , Álcool Feniletílico , Sirtuína 1 , Animais , Ratos , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Soluções para Diálise , Modelos Animais de Doenças , Homeostase/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/prevenção & controle , Peritônio/patologia , Peritônio/efeitos dos fármacos , Peritônio/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/efeitos dos fármacos , Sirtuína 1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
15.
Ecotoxicol Environ Saf ; 279: 116497, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38805827

RESUMO

Methamphetamine (METH) is a highly abused substance on a global scale and has the capacity to elicit toxicity within the central nervous system. The neurotoxicity induced by METH encompasses neuronal degeneration and cellular demise within the substantia nigra-striatum and hippocampus. Caffeic acid phenethyl ester (CAPE), a constituent of propolis, is a diminutive compound that demonstrates antioxidative and anti-inflammatory characteristics. Numerous investigations have demonstrated the safeguarding effects of CAPE in various neurodegenerative ailments. Our hypothesis posits that CAPE may exert a neuroprotective influence on METH-induced neurotoxicity via specific mechanisms. In order to validate the hypothesis, a series of experimental techniques including behavioral tests, immunofluorescence labeling, RNA sequencing, and western blotting were employed to investigate the neurotoxic effects of METH and the potential protective effects of CAPE. The results of our study demonstrate that CAPE effectively ameliorates cognitive memory deficits and anxiety symptoms induced by METH in mice. Furthermore, CAPE has been observed to attenuate the upregulation of neurotoxicity-associated proteins that are induced by METH exposure and also reduced the loss of hippocampal neurons in mice. Moreover, transcriptomics analysis was conducted to determine alterations in gene expression within the hippocampus of mice. Subsequently, bioinformatics analysis was employed to investigate the divergent outcomes and identify potential key genes. Interferon-stimulated gene 15 (ISG15) was successfully identified and confirmed through RT-qPCR, western blotting, and immunofluorescence techniques. Our research findings unequivocally demonstrated the neuroprotective effect of CAPE against METH-induced neurotoxicity, with ISG15 may have an important role in the underlying protective mechanism. These results offer novel perspectives on the treatment of METH-induced neurotoxicity.


Assuntos
Ácidos Cafeicos , Metanfetamina , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Álcool Feniletílico , Animais , Ácidos Cafeicos/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Metanfetamina/toxicidade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Camundongos , Masculino , Síndromes Neurotóxicas/prevenção & controle , Síndromes Neurotóxicas/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos
16.
Eur Rev Med Pharmacol Sci ; 28(8): 3288, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38708488

RESUMO

The article "The potential preventive role of a dietary supplement containing hydroxytyrosol in COVID-19: a multi-center study", by K. Dhuli, C. Micheletti, M.C. Medori, G. Madeo, G. Bonetti, K. Donato, F. Gaffuri, G.M. Tartaglia, S. Michelini, A. Fiorentino, D. Cesarz, S.T. Connelly, N. Capodicasa, M. Bertelli, published in Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 33-38-DOI: 10.26355/eurrev_202312_34687-PMID: 38112946 has been retracted by the Editor in Chief for the following reasons. Following some concerns raised on PubPeer, the Editor in Chief has started an investigation to assess the validity of the results. The outcome of the investigation revealed that the manuscript presented major flaws in the following: -       Issues with ethical approval -       Issues in methodology -       Undeclared conflict of interest Consequently, the Editor in Chief mistrusts the results presented and has decided to withdraw the article. The authors disagree with this retraction. https://www.europeanreview.org/article/34687 This article has been retracted. The Publisher apologizes for any inconvenience this may cause.


Assuntos
COVID-19 , Suplementos Nutricionais , Álcool Feniletílico , Álcool Feniletílico/análogos & derivados , Humanos , Álcool Feniletílico/administração & dosagem , Álcool Feniletílico/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2 , Tratamento Farmacológico da COVID-19
17.
Nutrients ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38732529

RESUMO

The Mediterranean diet, renowned for its health benefits, especially in reducing cardiovascular risks and protecting against diseases like diabetes and cancer, emphasizes virgin olive oil as a key contributor to these advantages. Despite being a minor fraction, the phenolic compounds in olive oil significantly contribute to its bioactive effects. This review examines the bioactive properties of hydroxytyrosol and related molecules, including naturally occurring compounds (-)-oleocanthal and (-)-oleacein, as well as semisynthetic derivatives like hydroxytyrosyl esters and alkyl ethers. (-)-Oleocanthal and (-)-oleacein show promising anti-tumor and anti-inflammatory properties, which are particularly underexplored in the case of (-)-oleacein. Additionally, hydroxytyrosyl esters exhibit similar effectiveness to hydroxytyrosol, while certain alkyl ethers surpass their precursor's properties. Remarkably, the emerging research field of the effects of phenolic molecules related to virgin olive oil on cell autophagy presents significant opportunities for underscoring the anti-cancer and neuroprotective properties of these molecules. Furthermore, promising clinical data from studies on hydroxytyrosol, (-)-oleacein, and (-)-oleocanthal urge further investigation and support the initiation of clinical trials with semisynthetic hydroxytyrosol derivatives. This review provides valuable insights into the potential applications of olive oil-derived phenolics in preventing and managing diseases associated with cancer, angiogenesis, and atherosclerosis.


Assuntos
Inibidores da Angiogênese , Azeite de Oliva , Fenóis , Álcool Feniletílico , Azeite de Oliva/química , Humanos , Fenóis/farmacologia , Inibidores da Angiogênese/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Dieta Mediterrânea , Aterosclerose/prevenção & controle , Aterosclerose/tratamento farmacológico , Monoterpenos Ciclopentânicos , Neoplasias/prevenção & controle , Neoplasias/tratamento farmacológico , Catecóis/farmacologia , Aldeídos/farmacologia , Animais , Antineoplásicos/farmacologia , Anti-Inflamatórios/farmacologia
18.
Molecules ; 29(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38792098

RESUMO

The olive oil industry recently introduced a novel multi-phase decanter with the "Leopard DMF" series, which gives a by-product called pâté, made up of pulp and olive wastewater with a high content of phenolic substances and without pits. This study aims to create a new culture medium, the Olive Juice Broth (OJB), from DMF pâté, and apply it to select bacteria strains able to survive and degrade the bitter substances normally present in the olive fruit. Thirty-five different bacterial strains of Lactiplantibacillus plantarum from the CREA-IT.PE Collection of Microorganisms were tested. Seven strains characterized by ≥50% growth in OJB (B31, B137, B28, B39, B124, B130, and B51) showed a degradation of the total phenolic content of OJB ≥ 30%. From this set, L. plantarum B51 strain was selected as a starter for table olive production vs. spontaneous fermentation. The selected inoculant effectively reduced the debittering time compared to spontaneous fermentation. Hydroxytyrosol, derived from oleuropein and verbascoside degradation, and tyrosol, derived from ligstroside degradation, were produced faster than during spontaneous fermentation. The OJB medium is confirmed to be useful in selecting bacterial strains resistant to the complex phenolic environment of the olive fruit.


Assuntos
Meios de Cultura , Fermentação , Olea , Fenóis , Olea/microbiologia , Olea/metabolismo , Olea/química , Fenóis/metabolismo , Fenóis/química , Meios de Cultura/química , Lactobacillales/metabolismo , Azeite de Oliva/química , Azeite de Oliva/metabolismo , Álcool Feniletílico/metabolismo , Álcool Feniletílico/química , Álcool Feniletílico/análogos & derivados , Glucosídeos Iridoides/metabolismo , Glucosídeos/metabolismo , Glucosídeos/química , Lactobacillus plantarum/metabolismo , Polifenóis
19.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732018

RESUMO

Hydroxytyrosol (HT) is a bioactive olive oil phenol with beneficial effects in a number of pathological situations. We have previously demonstrated that an HT-enriched diet could serve as a beneficial therapeutic approach to attenuate ischemic-stroke-associated damage in mice. Our exploratory pilot study examined this effect in humans. Particularly, a nutritional supplement containing 15 mg of HT/day was administered to patients 24 h after the onset of stroke, for 45 days. Biochemical and oxidative-stress-related parameters, blood pressure levels, serum proteome, and neurological and functional outcomes were evaluated at 45 and 90 days and compared to a control group. The main findings were that the daily administration of HT after stroke could: (i) favor the decrease in the percentage of glycated hemoglobin and diastolic blood pressure, (ii) control the increase in nitric oxide and exert a plausible protective effect in oxidative stress, (iii) modulate the evolution of the serum proteome and, particularly, the expression of apolipoproteins, and (iv) be beneficial for certain neurological and functional outcomes. Although a larger trial is necessary, this study suggests that HT could be a beneficial nutritional complement in the management of human stroke.


Assuntos
Suplementos Nutricionais , Estresse Oxidativo , Álcool Feniletílico , Acidente Vascular Cerebral , Humanos , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Masculino , Acidente Vascular Cerebral/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Feminino , Idoso , Projetos Piloto , Pessoa de Meia-Idade , Pressão Sanguínea/efeitos dos fármacos , Óxido Nítrico/metabolismo
20.
Food Chem ; 453: 139642, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38788643

RESUMO

Caffeic acid phenethyl ester (CAPE) is a naturally occurring phenolic compound with various biological activities. However, poor water solubility and storage stability limit its application. In this context, sorghum peptides were used to encapsulate CAPE. Sorghum peptides could self-assemble into regularly spherical nanoparticles (SPNs) by hydrophobic interaction and hydrogen bonds. Solubility of encapsulated CAPE was greatly increased, with 9.44 times higher than unencapsulated CAPE in water. Moreover, the storage stability of CAPE in aqueous solution was significantly improved by SPNs encapsulation. In vitro release study indicated that SPNs were able to delay CAPE release during the process of gastrointestinal digestion. Besides, fluorescence quenching analysis showed that a static quenching existed between SPNs and CAPE. The interaction between CAPE and SPNs occurred spontaneously, mainly driven by hydrophobic interactions. The above results suggested that SPNs encapsulation was an effective approach to improve the water solubility and storage stability of CAPE.


Assuntos
Ácidos Cafeicos , Nanopartículas , Peptídeos , Álcool Feniletílico , Solubilidade , Sorghum , Ácidos Cafeicos/química , Sorghum/química , Peptídeos/química , Nanopartículas/química , Álcool Feniletílico/química , Álcool Feniletílico/análogos & derivados , Interações Hidrofóbicas e Hidrofílicas , Estabilidade de Medicamentos , Composição de Medicamentos , Ligação de Hidrogênio , Tamanho da Partícula
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