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1.
PLoS One ; 13(10): e0204948, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30286181

RESUMO

This study evaluates whether intrathecal MVIIA injection after spinal cord injury (SCI) elicits neuroprotective effects. The test rats were randomly distributed into six groups- sham, placebo, MVIIA 2.5 µM, MVIIA 5 µM, MVIIA 10 µM, and MVIIA 20 µM-and were administered the treatment four hours after SCI. After the optimal MVIIA dose (MVIIA 10 µM) was defined, the best time for application, one or four hours, was analyzed. Locomotor hind limb function and side effects were assessed. Forty-eight hours after the injury and immediately after euthanasia, spinal cord segments were removed from the test rats. Cell viability, reactive oxygen species, lipid peroxidation, and glutamate release were investigated. To examine the MVIIA mechanism of action, the gene expressions of pro-apoptotic (Bax, nNOS, and caspase-3, -8, -9, -12) and anti-apoptotic (Bcl-xl) factors in the spinal cord tissue samples were determined by real-time PCR, and the activities of antioxidant enzymes were also investigated. Application of intrathecal MVIIA 10 µM four hours after SCI prompted a neuroprotective effect: neuronal death decreased (22.46%), oxidative stress diminished, pro-apoptotic factors (Bax, nNOS, and caspase-3, -8) were expressed to a lesser extent, and mitochondrial viability as well as anti-apoptotic factor (Bcl-xl) expression increased. These results suggested that MVIIA provided neuroprotection through antioxidant effects. Indeed, superoxide dismutase (188.41%), and glutathione peroxidase (199.96%), reductase (193.86%), and transferase (175.93%) expressions increased. Therefore, intrathecal MVIIA (MVIIA 10 µM, 4 h) application has neuroprotective potential, and the possible mechanisms are related to antioxidant agent modulation and to intrinsic and extrinsic apoptotic pathways.


Assuntos
Antioxidantes/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Conotoxinas/farmacologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Animais , Conotoxinas/efeitos adversos , Conotoxinas/uso terapêutico , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo
2.
Curr Drug Discov Technol ; 14(2): 127-134, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28000555

RESUMO

BACKGROUND: Propolis has been used as a natural health product mainly due to the presence of polyphenols, flavonoids, phenolic aldehydes, amino acids, vitamins and others bioactive constituents. To this natural substance are attributed different biological and pharmacological properties which are influenced by its chemical composition and organoleptic properties. The aim of this work was to evaluate the physicochemical properties and parameters of green propolis collected during a period of six years (2008-2013) in the state of Minas Gerais, located at the southeastern region of Brazil. METHODS: The methodology were in accordance with Brazilian legislation on the identity and quality standards of propolis. The evaluated parameters of hydroalcoholic from green propolis were total flavonoids, antioxidant activity - DPPH method, oxidation index, wax content, humidity and insoluble impurities. RESULTS: Propolis samples collected in different seasons during the years 2008 to 2013 presented mean values of total flavonoids (3.4 ± 0.11 mg/g), antioxidant activity DPPH (4.76 ± 0.16 µg/mL), oxidation index (3, 4 ± 0.33 seconds) and wax (15.14 ± 0.78% m/m), which are in accordance with Brazilian legislation. CONCLUSION: Green propolis did not show abrupt seasonal changes during the six years of investigation, and may be considered as an adequate functional ingredient.


Assuntos
Própole/química , Antioxidantes/química , Baccharis , Compostos de Bifenilo/química , Brasil , Flavonoides/análise , Fenóis/análise , Picratos/química , Estações do Ano , Ceras/análise
3.
Artigo em Inglês | MEDLINE | ID: mdl-25944116

RESUMO

Sulforaphane (SFN) is a molecule within the isothiocyanate (ITC) group of organosulfur compounds. SFN is a phytochemical commonly found in cruciferous vegetables such as broccoli, brussels sprouts and cabbages. It has been widely studied in order to evaluate its chemopreventive properties and some of those have already been established by means of animal and human models. The SFN induces Phase I and II enzymes involved in detoxification processes of chemical carcinogens in order to prevent the start of carcinogenesis. It also presents anti-tumor action at post-initiation Phase, suggesting supplementary roles in cancer prevention. In a dose dependent manner, ITC inhibits the viability of human cancer cells, modifies epigenetic events that occur in cancer cells and present antiinflammatory effect acting during the initial of uncontrolled cell proliferation. This protective effect may be due to its antioxidant status, its recognized capacity to induce the expression and/or activity of of different cytoprotective proteins involved in the activating "Nuclear factor erythroid-derived 2-like 2" (Nrf2). Nevertheless, the effects on health and the possible connections among different diet constituents in humans must be carefully studied as there are limitations in the current data in order to better understand the molecular mechanisms responsible for those effects. This survey also includes relevant patents on the use of SFN, like its use in skin cancer treatment (US2015038580); and as an adjuvant in anti-cancer treatment (US2014228419). The use of SFN as an antioxidant dietary supplement, methods for compositions that promote glutathione production (WO2015002279) and methods for extracting and purifying SFN from broccoli seeds (CN104086469) are also included in this review.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Isotiocianatos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antioxidantes/efeitos adversos , Antioxidantes/química , Apoptose/efeitos dos fármacos , Suplementos Nutricionais/efeitos adversos , Desenho de Fármacos , Epigênese Genética/efeitos dos fármacos , Humanos , Isotiocianatos/efeitos adversos , Isotiocianatos/química , Estrutura Molecular , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Patentes como Assunto , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Sulfóxidos
4.
Artigo em Inglês | MEDLINE | ID: mdl-24948024

RESUMO

Propolis is a resinous material collected by honeybees from numerous plants and serves as a defense against intruders. Because of its relevant curative properties, it is now gaining popularity in health foods and in cosmetic products. Understanding the underlying molecular mechanisms of phytochemicals has become a good strategy in bioprospection for new anti-inflammatory compounds. The biological activity of propolis derives from its high levels of phenolic acids, while flavonoids are thought to account for the activity of propolis extracts. The comprehension of the relationship between propolis and the immune system has progressed in the last years, recent articles have provided important contributions to this investigation field. Studies have shown that propolis suppressed the "IL-6-induced phosphorylation of signal transducer and STAT3", an essential cytokine-activated transcription factor in Th17 development. Therefore, action mechanisms of "propolis on Th17 differentiation could be instrumental in controlling disturbed cytokine networks in inflammation, autoimmune diseases, and infections." The use of propolis has been proposed in some patents as: WO201363714; CN102885854, WO2013142936, US20130266521, and US20130129808, which are related to the treatment of dental diseases; adjuvant in anti-cancer treatment; in cosmetic products; as an anti-inflammatory agent and natural antibiotic. Although there are many publications regarding the propolis efficacy, its applicability to human health and mechanisms of action are not completely understood, creating opportunities for new studies.


Assuntos
Fatores Imunológicos/imunologia , Fatores Imunológicos/uso terapêutico , Imunomodulação , Própole/imunologia , Própole/uso terapêutico , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Patentes como Assunto , Fosforilação , Fator de Transcrição STAT3/metabolismo , Células Th17/imunologia , Células Th17/metabolismo
5.
Cell Mol Neurobiol ; 34(1): 71-81, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24081560

RESUMO

GABA is an inhibitory neurotransmitter that appears to be associated with the action of volatile anesthetics. These anesthetics potentiate GABA-induced postsynaptic currents by synaptic GABAA receptors, although recent evidence suggests that these agents also significantly affect extrasynaptic GABA receptors. However, the effect of volatile anesthetics on the extracellular concentration of GABA in the central nervous system has not been fully established. In the present study, rat brain cortical slices loaded with [(3)H]GABA were used to investigate the effect of halothane and sevoflurane on the extracellular accumulation of this neurotransmitter. The accumulation of [(3)H]GABA was significantly increased by sevoflurane (0.058, 0.11, 0.23, 0.46, and 0.93 mM) and halothane (0.006, 0.012, 0.024, 0.048, 0072, and 0.096 mM) with an EC50 of 0.26 mM and 35 µM, respectively. TTX (blocker of voltage-dependent Na(+) channels), EGTA (an extracellular Ca(2+) chelator) and BAPTA-AM (an intracellular Ca(2+) chelator) did not interfere with the accumulation of [(3)H]GABA induced by 0.23 mM sevoflurane and 0.048 mM halothane. SKF 89976A, a GABA transporter type 1 (GAT-1) inhibitor, reduced the sevoflurane- and halothane-induced increase in the accumulation of GABA by 57 and 63 %, respectively. Incubation of brain cortical slices at low temperature (17 °C), a condition that inhibits GAT function and reduces GABA release through reverse transport, reduced the sevoflurane- and halothane-induced increase in the accumulation of [(3)H]GABA by 82 and 75 %, respectively, relative to that at normal temperature (37 °C). Ouabain, a Na(+)/K(+) ATPase pump inhibitor, which is known to induce GABA release through reverse transport, abolished the sevoflurane and halothane effects on the accumulation of [(3)H]GABA. The effect of sevoflurane and halothane did not involve glial transporters because ß-alanine, a blocker of GAT-2 and GAT-3, did not inhibit the effect of the anesthetics. In conclusion, the present study suggests that sevoflurane and halothane increase the accumulation of GABA by inducing the reverse transport of this neurotransmitter. Therefore, volatile anesthetics could interfere with neuronal excitability by increasing the action of GABA on synaptic and extrasynaptic GABA receptors.


Assuntos
Anestésicos/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Ácido gama-Aminobutírico/metabolismo , Anestésicos/administração & dosagem , Animais , Cálcio/farmacologia , Temperatura Baixa , Halotano/administração & dosagem , Halotano/farmacologia , Éteres Metílicos/administração & dosagem , Éteres Metílicos/farmacologia , Ácidos Nipecóticos/farmacologia , Ouabaína/farmacologia , Ratos , Sevoflurano , Tetrodotoxina/toxicidade , Trítio/metabolismo , Volatilização , beta-Alanina/farmacologia
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