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1.
Exp Parasitol ; 214: 107904, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32371061

RESUMO

Hydatidosis or cystic echinococcosis is a disease caused by the larval stage of Echinococcus granulosus sensu lato. Chemotherapy can be used alone or in combination with surgery or percutaneous treatment. Benzimidazoles are the only agents used and approved for treatment, but their efficacy is extremely variable. Therefore, it is necessary to find new drugs to improve the treatment of this disease. In the last decades, the biological properties of essential oils and their components began to be investigated as alternatives in the treatment of different ailments. The aim of the present work was to evaluate the in vitro efficacy of the essential oil of Cinnamomum zeylanicum (cinnamon) and cinnamaldehyde against protoscoleces and metacestodes of E. granulosus. The essential oil and cinnamaldehyde, its major component, showed a dose and time dependent effect against protoscoleces. However, cinnamaldehyde showed a greater protoscolicidal effect than the essential oil. The maximum protoscolicidal effect was found with 50 µg/mL of cinnamaldehyde. Viability decreased by 1.7 ± 0.8% after 4 days of incubation and reached 0% at 8 days. Interestingly, there were no significant differences between the activity of cinnamaldehyde at the concentrations of 25 and 10 µg/mL and the efficacy observed with the essential oil at 200 and 50 µg/mL, respectively. Cinnamaldehyde also had a strong in vitro effect against murine cysts, while only the higher concentration of the essential oil caused ultrastructural alterations. Working with components instead of with essential oils has some advantages, particularly in relation to the reproducibility of the formulations and their effectiveness. For this reason, the results obtained in this work are promising in the search for pharmaceutical alternatives for the treatment of cystic echinococcosis.


Assuntos
Acroleína/análogos & derivados , Anticestoides/farmacologia , Cinnamomum zeylanicum/química , Echinococcus granulosus/efeitos dos fármacos , Óleos Voláteis/farmacologia , Acroleína/farmacologia , Animais , Equinococose/tratamento farmacológico , Echinococcus granulosus/crescimento & desenvolvimento , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento
2.
Food Microbiol ; 87: 103388, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31948629

RESUMO

The growing demand for minimally processed foods with clean labels has stimulated research into mild processing methods and natural antimicrobials to replace intensive heating and conventional preservatives, respectively. However, we have previously demonstrated that repetitive exposure of some bacteria to mild heat or subinhibitory concentrations of essential oil constituents (EOCs) may induce the emergence of mutants with increased resistance to these treatments. Since the combination of mild heat with some EOCs has a synergistic effect on microbial inactivation, we evaluated the potential of such combinations against our resistant E. coli mutants. While citral, carvacrol and t-cinnamaldehyde synergistically increased heat inactivation (53.0 °C, 10 min) of the wild-type MG1655 suspended in buffer, only the combination with carvacrol (200 µl/l) was able to mitigate the increased resistance of all the mutants. Moreover, the combination of heat and carvacrol acted synergistically inactivating heat-resistant variants of E. coli O157:H7 (ATCC 43888). This combined treatment could synergistically achieve more than 5 log10 reductions of the most resistant mutants in coconut water, although the temperature had to be raised to 57.0 °C. Therefore, the combination of mild heat with carvacrol appears to hold promise for mild processing, and it is expected to counteract the development of heat resistance.


Assuntos
Antibacterianos/farmacologia , Cocos/química , Escherichia coli O157/efeitos dos fármacos , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos Vegetais/farmacologia , Acroleína/análogos & derivados , Acroleína/farmacologia , Monoterpenos Acíclicos/farmacologia , Cimenos/farmacologia , Farmacorresistência Bacteriana , Escherichia coli O157/crescimento & desenvolvimento , Temperatura Alta
3.
J Food Sci ; 85(1): 157-164, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31909483

RESUMO

Campylobacter species are known as biofilm-forming bacteria in food systems. The aim of this study was to evaluate the antimicrobial and antibiofilm effects of cinnamaldehyde against Campylobacter jejuni and Campylobacter coli isolated from chicken meat. The biofilm-forming C. jejuni and C. coli strains from chicken meat were investigated using minimum inhibitory concentration (MIC) and Campylobacter spp. characteristics. The MIC value was 31.25 µg/mL for the Campylobacter strains tested. Cinnamaldehyde had an inhibition and degradation effect on Campylobacter biofilms at concentrations > 15.63 µg/mL. Campylobacter strains treated with 15.63 µg/mL CA exhibited significantly decreased autoaggregation, motility, exopolysaccharide production, and soluble protein. In addition, Campylobacter biofilms formed on stainless steel were degraded following cinnamaldehyde treatment, as determined by scanning electron microscopy. Taken together, these results suggest that cinnamaldehyde constitutes a potential natural preservative against Campylobacter and a nontoxic biofilm remover that could be applied to control food poisoning in the poultry manufacturing-related food industry. PRACTICAL APPLICATION: Cinnamaldehyde was able to effectively remove the biofilm of Campylobacter in the small crack of stainless steel. Cinnamaldehyde has a potential to replace the synthetic antimicrobial and/or antibiofilm agent as well as has a positive influence on consumer concern for the food safety issues of the poultry industries.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Campylobacter coli/efeitos dos fármacos , Acroleína/farmacologia , Animais , Bactérias/efeitos dos fármacos , Campylobacter coli/fisiologia , Campylobacter jejuni/efeitos dos fármacos , Galinhas/microbiologia , Carne/microbiologia , Testes de Sensibilidade Microbiana , Aço Inoxidável/análise
4.
Chemistry ; 26(8): 1871-1879, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31804737

RESUMO

Mounting evidence supports the role of amyloidogenesis, oxidative stress, and metal dyshomeostasis in the development of neurodegenerative disorders. Parkinson's Disease is characterized by α-synuclein (αSyn) accumulation and aggregation in brain regions, also promoted by Cu2+ . αSyn is modified by reactive carbonyl species, including acrolein (ACR). Notwithstanding these findings, the interplay between ACR, copper, and αSyn has never been investigated. Therefore, we explored more thoroughly the effects of ACR on αSyn using an approach based on LC-MS/MS analysis. We also evaluated the influence of Cu2+ on the protein carbonylation and how the ACR modification impacts the Cu2+ binding and the production of Reactive Oxygen Species (ROS). Finally, we investigated the effects of ACR and Cu2+ ions on the αSyn aggregation by dynamic light scattering and fluorescence assays. Cu2+ regioselectively inhibits the modification of His50 by ACR, the carbonylation lowers the affinity of His50 for Cu2+ and ACR inhibits αSyn aggregation both in the presence and in the absence of Cu2+ .


Assuntos
Acroleína/química , Cobre/química , alfa-Sinucleína/química , Acroleína/farmacologia , Cromatografia Líquida de Alta Pressão , Cobre/farmacologia , Difusão Dinâmica da Luz , Humanos , Estresse Oxidativo/efeitos dos fármacos , Agregados Proteicos/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas em Tandem , alfa-Sinucleína/análise , alfa-Sinucleína/metabolismo
5.
Int J Mol Sci ; 21(1)2019 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-31877837

RESUMO

The effects of trans-cinnamaldehyde (TC) on transcriptional profiles of biofilm-associated genes and the metabolic activity of two methicillin-resistant Staphylococcus aureus (MRSA) strains showing a different degree of adherence to polystyrene, were evaluated. Metabolic activity of S. aureus in biofilm was significantly decreased in the presence of TC at 1/2 minimum biofilm inhibition concentration (MBIC). Expression levels of the genes encoding laminin binding protein (eno), elastin binding protein (ebps) and fibrinogen binding protein (fib) in the presence of TC at 1/2 MBIC were lower than in untreated biofilm in both the weakly and strongly adhering strain. The highest decrease of expression level was observed in case of fib in the strongly adhering strain, in which the amount of fib transcript was 10-fold lower compared to biofilm without TC. In the presence of TC at 1/2 MBIC after 3, 6, 8 and 12 h, the expression level of icaA and icaD, that are involved in the biosynthesis of polysaccharide intercellular adhesin, was above half lower in the weakly adhering strain compared to biofilm without TC. In the strongly adhering strain the highest decrease in expression of these genes was observed after 3 and 6 h. This study showed that TC is a promising anti-biofilm agent for use in MRSA biofilm-related infections.


Assuntos
Acroleína/análogos & derivados , Biofilmes/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Genes Bacterianos/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Acroleína/química , Acroleína/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/fisiologia , Testes de Sensibilidade Microbiana/métodos , Polissacarídeos Bacterianos/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle
6.
Vet Microbiol ; 239: 108463, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767076

RESUMO

The increasing understanding of bacterial pathogenesis has revealed many new targets for the development of non-traditional antibacterial drugs. Interference with bacterial virulence has become a new strategy to treat bacteria-mediated diseases. As an important food-borne pathogen, Salmonella enterica serovar Typhimurium uses type III secretion system (T3SS) to facilitate invasion of host cells. In this study, we identified cinnamaldehyde as a Salmonella pathogenicity island 1 (SPI-1) inhibitor which blocks the secretion of several SPI-1 associated effector proteins and consequently exhibits a strong inhibitory effect on SPI-1-mediated invasion of HeLa cells. Further study revealed that cinnamaldehyde significantly reduced the transcription of some SPI-1 genes, such as sipA and sipB, in S. Typhimurium by affecting multiple SPI-1 regulator genes. In an animal infection model, cinnamaldehyde effectively protected infected mice against S. Typhimurium-induced mortality and pathological damages. In summary, this study presented an effective SPI-1 inhibitor, cinnamaldehyde, which reduces the expression of SPI-1 effector proteins by regulating the transcription of main regulator genes.


Assuntos
Acroleína/análogos & derivados , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Sistemas de Secreção Tipo III/efeitos dos fármacos , Acroleína/farmacologia , Acroleína/uso terapêutico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Modelos Animais de Doenças , Células HeLa , Humanos , Camundongos , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/mortalidade
7.
World J Microbiol Biotechnol ; 35(12): 183, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728740

RESUMO

Caffeine is a naturally occurring alkaloid, where its major consumption occurs with beverages such as coffee, soft drinks and tea. Despite a variety of reports on the effects of caffeine on diverse organisms including yeast, the complex molecular basis of caffeine resistance and response has yet to be understood. In this study, a caffeine-hyperresistant and genetically stable Saccharomyces cerevisiae mutant was obtained for the first time by evolutionary engineering, using batch selection in the presence of gradually increased caffeine stress levels and without any mutagenesis of the initial population prior to selection. The selected mutant could resist up to 50 mM caffeine, a level, to our knowledge, that has not been reported for S. cerevisiae so far. The mutant was also resistant to the cell wall-damaging agent lyticase, and it showed cross-resistance against various compounds such as rapamycin, antimycin, coniferyl aldehyde and cycloheximide. Comparative transcriptomic analysis results revealed that the genes involved in the energy conservation and production pathways, and pleiotropic drug resistance were overexpressed. Whole genome re-sequencing identified single nucleotide polymorphisms in only three genes of the caffeine-hyperresistant mutant; PDR1, PDR5 and RIM8, which may play a potential role in caffeine-hyperresistance.


Assuntos
Cafeína/farmacologia , Farmacorresistência Fúngica/genética , Engenharia de Proteínas/métodos , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Transportadores de Cassetes de Ligação de ATP/genética , Acroleína/análogos & derivados , Acroleína/farmacologia , Antimicina A/análogos & derivados , Antimicina A/farmacologia , Proteínas de Ciclo Celular/genética , Cicloeximida/farmacologia , Proteínas de Ligação a DNA/genética , Mutagênese , Polimorfismo de Nucleotídeo Único , Proteínas de Saccharomyces cerevisiae/genética , Sirolimo/farmacologia , Estresse Fisiológico , Fatores de Transcrição/genética , Transcriptoma , Sequenciamento Completo do Genoma
8.
Fitoterapia ; 139: 104405, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31707126

RESUMO

There is a continuing rise in the occurrence of multidrug-resistant bacterial infections. Antibiotic resistance to currently available antibiotics has become a global health issue leading to an urgent need for alternative antibacterial strategies. There has been a renewed interest in the development of antibacterial agents from natural sources, and trans-cinnamaldehyde is an example of a naturally occurring compound that has received significant attention in recent years. Trans-Cinnamaldehyde has been shown to possess substantial antimicrobial activity, as well as an array of other medicinal properties, and represents an intriguing hit compound from which a number of derivatives have been developed. In some cases, these derivatives have been shown to possess improved activity, not only compared to trans-cinnamaldehyde but also to commonly used antibiotics. Therefore, understanding the antibacterial mechanisms of action that these compounds elicit is imperative in order to facilitate their development and the development of new antibacterial agents that could exploit similar mechanistic approaches. The purpose of this review is to provide an overview of current knowledge on the antibacterial activity and mechanisms of action of cinnamaldehyde and its derivatives, and to highlight significant contributions made in this research area. It is hoped that the findings presented in this work will aid the future development of new antibacterial agents.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Acroleína/química , Acroleína/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Cinnamomum/química , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Casca de Planta/química
9.
Carbohydr Polym ; 226: 115298, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582068

RESUMO

Traditional method of chitosan (naturally available abundant biopolymer) nanoparticles synthesis is the ionic cross-linking between chitosan and say, sodium tri-polyphosphate (TPP). These nanoparticles are structurally less stable and are basically obtained viaconversion of chitosan, a pure bio-based material, into a hybrid structure of biopolymer and a synthetic chemical. The present work reports a novel attempt to synthesize antimicrobial chitosan nanoparticles by chemical cross-linking with cinnamaldehyde, another eco-friendly bactericidal agent. The synthesized nanoparticles (size range, 80-150 nm) were analysed for their surface morphology. X-ray diffraction pattern denoted the amorphous characteristics of the formed nanoparticles. The FTIR analysis revealed formulation of chitosan nanoparticles to be based on Schiff reaction between amino group of chitosan and aldehyde group of cinnamaldehyde. NMR analysis also confirmed the formulation of cinnamaldehyde cross-linked chitosan nanoparticles. TGA and DSC were performed to analyse thermal characteristics and stability of prepared nanoparticles. Subsequently, the study successfully indicated that the synthesized nanoparticles exhibit synergistic antibacterial activity (98%) against Staphylococcus aureus (Gram-positive) and (96%) Escherichia coli (Gram-negative) bacteria. The MIC and MBC values were found to be 5 mg/mL and 10 mg/mL, respectively, for both types of bacteria.


Assuntos
Acroleína/análogos & derivados , Antibacterianos , Quitosana , Escherichia coli/efeitos dos fármacos , Nanopartículas/química , Staphylococcus aureus/efeitos dos fármacos , Acroleína/química , Acroleína/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Quitosana/farmacologia
10.
Invest Ophthalmol Vis Sci ; 60(13): 4425-4435, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31652327

RESUMO

Purpose: To investigate the effect of the unsaturated aldehyde acrolein on retinal glial cell migration. Methods: Müller glial cell markers expression in TR-MUL5 were confirmed by RT-PCR and immunostaining. Cell viability and migration rate of TR-MUL5 cells were assessed after the stimulation with acrolein. DNA microarray analysis was performed to analyze changes in the expression levels of migration-related genes in Müller glial cells stimulated with acrolein. Real-time PCR and ELISA were performed to validate DNA microarray analysis results. Inhibitors of C-X-C motif chemokine ligand 1 (CXCL1), one of the genes highly upregulated after the exposure to acrolein, and blockers of its receptor, CXCR2, were used to investigate the role of the CXCL1-CXCR2 axis on glial cell migration. CXCL1 concentration was measured in vitreous fluid samples obtained from proliferative diabetic retinopathy (PDR) and nondiabetic control eyes. CXCL1 and CXCR2 expression in glial cells of fibrovascular tissues obtained from PDR patients was examined by immunostaining. Results: At a high concentration, acrolein (100 µM) significantly decreased cell viability. However, in moderate, sublethal concentrations (25-50 µM), acrolein induced cell migration and substantially increased the production of CXCL1 in TR-MUL5 cells. CXCL1 concentration was significantly elevated in vitreous fluids of PDR patients, and CXCL1 and CXCR2 were present in glial cells in fibrovascular tissues of PDR patients. CXCL1 stimulation increased glial cell migration in a dose-dependent manner, which was abrogated by the neutralization of the CXCL1-CXCR2 axis. Conclusions: Our data demonstrate that acrolein promotes retinal Müller glial cell migration by enhancing CXCL1 production.


Assuntos
Acroleína/farmacologia , Movimento Celular/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroglia/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Ratos Transgênicos , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo , Corpo Vítreo/metabolismo
11.
J Agric Food Chem ; 67(42): 11638-11649, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31532204

RESUMO

Naturally occurring cinnamon compounds such as cinnamaldehyde (CAL) and structurally related constituents have been associated with antiobesity activities, although studies regarding the impact on intestinal fatty acid uptake are scarce. Here, we demonstrate the effects of CAL and structural analogues cinnamyl alcohol (CALC), cinnamic acid (CAC), and cinnamyl isobutyrate on mechanisms regulating intestinal fatty acid uptake in differentiated Caco-2 cells. CAL, CALC, and CAC (3000 µM) were found to decrease fatty acid uptake by 58.0 ± 8.83, 19.4 ± 8.98, and 21.9 ± 6.55%, respectively. While CAL and CALC at a concentration of 300 µM increased serotonin release 14.9 ± 3.00- and 2.72 ± 0.69-fold, respectively, serotonin alone showed no effect on fatty acid uptake. However, CAL revealed transient receptor potential channel A1-dependency in the decrease of fatty acid uptake, as well as in CAL-induced serotonin release. Overall, CAL was identified as the most potent of the cinnamon constituents tested.


Assuntos
Acroleína/análogos & derivados , Cinamatos/farmacologia , Cinnamomum zeylanicum/química , Ácidos Graxos/metabolismo , Extratos Vegetais/farmacologia , Propanóis/farmacologia , Acroleína/química , Acroleína/farmacologia , Transporte Biológico/efeitos dos fármacos , Células CACO-2 , Diferenciação Celular , Cinamatos/química , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Extratos Vegetais/química , Propanóis/química
12.
J Agric Food Chem ; 67(40): 11066-11076, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508948

RESUMO

The electrospinning of nanofibers (NFs) of cinnamaldehyde inclusion complexes (ICs) with two different hydroxypropylated cyclodextrins (CDs), hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD), was successfully performed in order to produce cinnamaldehyde/CD-IC NFs without using an additional polymer matrix. The inclusion complexation between cinnamaldehyde and hydroxypropylated CDs was studied by computational molecular modeling, and the results suggested that HP-ß-CD and HP-γ-CD can be inclusion complexed with cinnamaldehyde at 1:1 and 2:1 (cinnamaldehyde/CD) molar ratios. Additionally, molecular modeling and phase solubility studies showed that water solubility of cinnamaldehyde dramatically increases with cyclodextrin inclusion complex (CD-IC) formation. The HP-ß-CD has shown slightly stronger binding with cinnamaldehyde when compared to HP-γ-CD for cinnamaldehyde/CD-IC. Although cinnamaldehyde is a highly volatile compound, it was effectively preserved with high loading by the cinnamaldehyde/CD-IC NFs. It was also observed that cinnamaldehyde has shown much higher temperature stability in cinnamaldehyde/CD-IC NFs compared to uncomplexed cinnamaldehyde because of the inclusion complexation state of cinnamaldehyde within the hydroxypropylated CD cavity. Moreover, cinnamaldehyde still has kept its antibacterial activity in cinnamaldehyde/CD-IC NF samples when tested against Escherichia coli. In addition, cinnamaldehyde/CD-IC NF mats were fast-dissolving in water, even though pure cinnamaldehyde has a water-insoluble nature. In brief, self-standing nanofibrous mats of electrospun cinnamaldehyde/CD-IC NFs are potentially applicable in food, oral-care, healthcare, and pharmaceutics because of their fast-dissolving character, enhanced water solubility, stability at elevated temperature, and promising antibacterial activity.


Assuntos
Acroleína/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacologia , Composição de Medicamentos/métodos , Acroleína/química , Acroleína/farmacologia , Ciclodextrinas/química , Composição de Medicamentos/instrumentação , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Nanofibras/química , Solubilidade , Temperatura
13.
Int J Nanomedicine ; 14: 5713-5728, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413571

RESUMO

Purpose: The levels of reactive oxygen species (ROS) in tumor cells are much higher than that in normal cells, and rise rapidly under the influence of exogenous or endogenous inducing factors, eventually leading to the apoptosis of tumor cells. Therefore, this study prepared a dual pH/reducing-responsive poly (N-isopropylacrylamide-co-Cinnamaldehyde-co-D-α-tocopheryl polyethylene glycol 1000 succinate, PssNCT) nanogels, which employed two exogenous ROS inducers, cinnamaldehyde (CA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), to selectively induce apoptosis by regulating ROS levels in tumor cells. Methods: The PssNCT nanogels were prepared by the free radical precipitation polymerization under the crosslink between pH-sensitive hydrazone and reducing-sensitive disulfide bonds, followed by the physicochemical and morphological characteristics investigations. Plasma stability, dual pH/reducing responsive degradation and in vitro release were also assessed. In cell experiments, cytotoxicity in different cells were first detected. The intracellular ROS levels and mitochondrial functions of tumor cells were then evaluated. Moreover, the apoptosis and western-blot assays were employed to verify the association between ROS levels elevation and apoptosis in tumor cells. Results: The nanogels exhibited a round-like hollow structure with the diameter smaller than 200nm. The nanogels were stable in plasma, while showed rapid degradation in acidic and reducing environments, thus achieving significant release of CA and TPGS in these media. Furthermore, the sufficient amplification of ROS signals was induced by the synergistically function of CA and TPGS on mitochondria, which resulted in the opening of the mitochondrial apoptotic pathway and enhanced cytotoxicity on MCF-7 cells. However, nanogels barely affected L929 cells owing to their lower intracellular ROS basal levels. Conclusion: The specific ROS regulation method achieved by these nanogels could be explored to selectively kill tumor cells according to the difference of ROS signals in different kinds of cells.


Assuntos
Apoptose , Espaço Intracelular/química , Polietilenoglicóis/farmacologia , Polietilenoimina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acroleína/análogos & derivados , Acroleína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Vitamina E/síntese química , Vitamina E/química
14.
Int Braz J Urol ; 45(5): 1033-1042, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31408283

RESUMO

Cinnamomum cassia (Cinnamon) is a well-known traditional medicine with therapeutic benefits for centuries. We evaluated the effects of cinnamon essential oil (CEO) and its main component cinnamaldehyde (CA) on human corpus cavernosum (HCC) and rat CC. The essential oil of cinnamon was analyzed for the confirmation of the oil profile. HCC specimens from patients undergoing penile prosthesis surgery (age 48-69 years) were utilized for functional studies. In addition, erectile responses in anesthetized control and diabetic rats were evaluated in vivo after intracavernosal injection of CEO and CA, and rat CC strips were placed in organ baths. After precontraction with phenylephrine (10µM), relaxant responses to CEO and CA were investigated. CA (96.9%) was found as the major component. The maximum relaxation responses to CEO and CA were 96.4±3.5% and 96.0±5.0% in HCC and 97.5±5.5% and 96.8±4.8% in rat CC, respectively. There was no difference between control and diabetic rats in relaxation responses to CEO and CA. The relaxant responses obtained with essential oil and CA were not attenuated in the presence of nitric oxide synthase (NOS) inhibitor, and soluble guanylate cyclase inhibitor (sGS) in CC. In vivo, erectile responses in diabetic rats were lower than in control rats, which was restored after intracavernosal injection of CEO and CA. CEO and CA improved erectile function and relaxation of isolated strips of rat CC and HCC by a NO/cGMP-independent mechanism. Further investigations are warranted to fully elucidate the restorative effects of CEO and CA on diabetic erectile dysfunction.


Assuntos
Acroleína/análogos & derivados , Cinnamomum zeylanicum/química , Relaxamento Muscular/efeitos dos fármacos , Óleos Voláteis/farmacologia , Pênis/efeitos dos fármacos , Acroleína/farmacologia , Idoso , Análise de Variância , Animais , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Relaxamento Muscular/fisiologia , Ereção Peniana/efeitos dos fármacos , Ereção Peniana/fisiologia , Pênis/fisiopatologia , Fenilefrina/farmacologia , Inibidores da Fosfodiesterase 5/farmacologia , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Citrato de Sildenafila/farmacologia , Vasoconstritores/farmacologia
15.
Eur J Pharmacol ; 859: 172530, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31283934

RESUMO

Cinnamon, a spice widely used in cuisine, has been reported to exert therapeutic effects. Recently, cinnamon was shown to improve memory in some animal models of memory impairment and in poor learning mice. This study aimed to investigate the effect of cinnamaldehyde, the major compound in cinnamon on passive avoidance memory and activation of hippocampal Akt (protein kinase B), ERK (extracellular signal-regulated kinase) and GSK-3ß (Glycogen Synthase Kinase-3beta) in mice. In the present study, oral cinnamaldehyde at doses of 12.5, 25, 30, 40, 45, 50 and 100 mg/kg/daily was administered to adult male NMRI mice, initiated 10 days before training and continued during training and retention days. Training of passive avoidance task was performed on day 10 and a retention trial was done 24 h after. Upon completion of the retention test, hippocampi were removed for Western blot analysis to detect the phosphorylated and total levels of Akt, ERK and GSK-3ß proteins. Results showed that cinnamaldehyde exerts a biphasic effect on passive avoidance memory by impairing memory at lower doses while improving at higher doses. Moreover, at memory improving doses, cinnamaldehyde increased the phosphorylated forms of hippocampal Akt, ERK and GSK-3ß while these proteins did not change at impairing doses of cinnamaldehyde. For the first time, this study revealed a biphasic effect of cinnamaldehyde on memory as well as indicating that the memory improving effect of higher doses of this substance is accompanied with hippocampal Akt, ERK and GSK-3ß signaling alterations in adult mice.


Assuntos
Acroleína/análogos & derivados , Aprendizagem da Esquiva/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Acroleína/farmacologia , Animais , Relação Dose-Resposta a Droga , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Camundongos , Fosforilação/efeitos dos fármacos
16.
Photochem Photobiol Sci ; 18(8): 2003-2011, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268087

RESUMO

Here we report the activatable photosensitizer BromoAcroB, a brominated BODIPY dye incorporating a reactive acrolein warhead. The acrolein moiety serves as an intramolecular switch, deactivating the BODIPY dye in its singlet and triplet excited states via internal conversion. Thiolate addition to this moiety disables the intramolecular quenching mechanism restoring the photosensitizing properties of the parent dye, characterized by a quantum yield of singlet oxygen photosensitization of 0.69 ± 0.02. In cell cultures, and upon thiol adduct formation, BromoAcroB induced light-dependent cell death in MRC-5 and HeLa cell lines. Using fluorescence microscopy and upon measuring the low yet non-negligible emission of the activated compound, we show that the phototoxicity of the dormant photosensitizer correlated with the quantity of BromoAcroB adducts generated. BromoAcroB thus serves as a dormant photosensitizer sensitive to intracellular electrophile response. Our results highlight the effective control of a triplet state process by modulation of an unsaturated moiety on the BODIPY scaffold and underscore the mechanistic opportunities arising for controlled singlet oxygen production in cells specifically sensitive to electrophile stress.


Assuntos
Acroleína/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Cisteína/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/farmacologia , Acroleína/química , Compostos de Boro/química , Morte Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cisteína/química , Células HeLa , Humanos , Luz , Microscopia de Fluorescência , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Teoria Quântica , Oxigênio Singlete/química
17.
J Chem Ecol ; 45(8): 667-672, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313134

RESUMO

Agriotes ustulatus is an economically important click beetle in Europe. A female-produced pheromone, (E,E)-farnesyl acetate, has been identified and is used for monitoring and detecting males. More recently, a floral lure targeting females with modest, but significant, activity has been described. Based on preliminary data, we hypothesized, that similar to the effects on the congeneric A. brevis, addition of the pheromone to the floral lure should improve female A. ustulatus catches. Also, as click beetles have been reported to respond to white light, we studied possible interactions between visual and chemical cues. In field trials, the addition of the synthetic pheromone to the floral lure resulted in a dramatic increase in the number of females trapped, whereas male catches remained unaffected and equal to those in traps baited with pheromone only. A white visual cue did not influence trap catches. Maximum catches of both sexes of A. ustulatus can be achieved using the pheromone and the floral lure inside the same trap. Furthermore, the compounds can be formulated in a single polyethylene bag dispenser, making handling of the trap easier. Due to a much larger proportion of females in the catch, this improved trap may be a promising tool for semiochemical-based, environmentally sound agricultural practice against this important pest.


Assuntos
Besouros/fisiologia , Feromônios/química , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Animais , Anisóis/química , Anisóis/farmacologia , Comportamento Animal/efeitos dos fármacos , Farneseno Álcool/análogos & derivados , Farneseno Álcool/química , Farneseno Álcool/farmacologia , Feminino , Flores/química , Flores/metabolismo , Controle de Insetos , Masculino , Feromônios/farmacologia , Estereoisomerismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-31294650

RESUMO

The present study examines the influence of the natural preservatives carvacrol, eugenol, trans-cinnamaldehyde and the essential oil (EO) Origanum vulgare on ochratoxin A (OTA) production and the mycelial growth of two food-related moulds, Penicillium verrucosum and Aspergillus westerdijkiae, by broth macro-dilution assay for 21 days. With the addition of ½ minimum inhibitory concentration (MIC) carvacrol, eugenol and O. vulgare EO, the mycelial dry weight of both moulds decreased significantly over the whole incubation period of 7, 14 and 21 days. Trans-cinnamaldehyde slightly stimulated the growth of A. westerdijkiae and P. verrucosum at 14 and 21 days of incubation. Growth inhibition did not accompany inhibition of OTA production. Although the growth of both moulds was inhibited after the addition of ½ MIC carvacrol, eugenol and O. vulgare EO, the OTA production of the strong mycotoxin producer A. westerdijkiae was stimulated. Only trans-cinnamaldehyde inhibited the production of OTA with the addition of ½ MIC. P. verrucosum produced significantly less OTA than A. westerdijkiae, and its mycotoxin production was almost completely inhibited by the addition of ½ MIC of the natural preservatives.


Assuntos
Aspergillus/efeitos dos fármacos , Microbiologia de Alimentos , Conservantes de Alimentos/farmacologia , Micélio/efeitos dos fármacos , Ocratoxinas/biossíntese , Penicillium/efeitos dos fármacos , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Aspergillus/química , Eugenol/química , Eugenol/farmacologia , Conservantes de Alimentos/química , Monoterpenos/química , Monoterpenos/farmacologia , Micélio/crescimento & desenvolvimento , Ocratoxinas/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Penicillium/química
19.
J Therm Biol ; 83: 54-59, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331525

RESUMO

The aim of this study was to examine the effect of estradiol (E2) on the thermoregulatory responses induced by cinnamaldehyde, a component extracted from cinnamon at 16 °C or 27 °C. The thermoneutral and subneutral experiments were performed to evaluate the augmented effect of cinnamaldehyde by cold exposure and the effect of cinnamaldehyde itself. Ovariectomized rats were implanted with a silastic tube with or without E2 (E2(+) and E2(-) groups), and data loggers into the peritoneal cavity. After the application of 30% cinnamaldehyde or vehicle into the skin of the whole trunk of rats, the rats were exposed to 16 °C or 27 °C for 2 h. Body temperature (Tb) and tail temperature (Ttail) were measured using a data logger and thermography. After exposure, blood samples were obtained, and plasma catecholamine concentration were measured by high-performance liquid chromatography. In the E2(-) group exposed to 27 °C, the change in Tb in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle. The change in Ttail in rats applied cinnamaldehyde was significantly lower than that of rats applied vehicle in both E2(-) and E2(+) groups at 27 °C and 16 °C. Plasma catecholamine concentration at 27 °C was not different among the groups. E2 might not affect thermoregulatory responses induced by cinnamaldehyde application; however, it decreased Ttail in female rats.


Assuntos
Acroleína/análogos & derivados , Temperatura Corporal/efeitos dos fármacos , Estradiol/farmacologia , Acroleína/farmacologia , Animais , Regulação da Temperatura Corporal , Feminino , Ratos , Ratos Wistar , Cauda/fisiologia
20.
Pharmacology ; 104(3-4): 207-211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31302651

RESUMO

The effects of cinnamaldehyde (CNA), known as a transient receptor potential ankyrin 1 (TRPA1) agonist, on guinea-pig ileum and urinary bladder were studied in isolated organ experiments. Contractile effects were found to be present on both preparations. In the ileum, both cholinergic and purinergic (pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium salt-sensitive) mechanisms are involved; the TRPA1 antagonist A967079 (1 µmol/L) significantly reduced the response. The contractile response to CNA in the bladder, but not in the ileum, was significantly reduced by in vitro capsaicin desensitization. In the bladder A967079 or the TRPV1 antagonist, BCTC failed to reduce the response. A direct relaxation on the smooth muscle was detected in the precontracted ileum. In the precontracted urinary bladder, CNA also caused relaxation that was insensitive to capsaicin pretreatment. It is suggested that CNA excites the muscles of the bladder via activation of capsaicin-sensitive nerves; in the ileum, it may interact with TRPA1 located on tissue elements that initiate both purinergic and cholinergic mechanisms. The relaxant effects of CNA may be due to the direct inhibition of the smooth muscles.


Assuntos
Acroleína/análogos & derivados , Músculo Liso/efeitos dos fármacos , Acroleína/farmacologia , Animais , Capsaicina/metabolismo , Feminino , Cobaias , Íleo/efeitos dos fármacos , Íleo/metabolismo , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Canais de Cátion TRPV/metabolismo , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo
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