Düsseldorf, Univ., Diss., 2002. / Computerdatei im Fernzugriff.

Düsseldorf, Univ., Diss., 2002. / Computerdatei im Fernzugriff.

Düsseldorf, Universiẗat, Diss., 2002.

No / Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Sustained activation of nuclear transcription factor κB (NF-κB) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-κB signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFα, 150 ng/ml) increased NF-κB-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative IκBα construct. In addition, TNFα increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-κB activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((−)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1–1 μM) for 18 h. None of the flavonoids modulated constitutive or TNFα-induced NF-κB activity. Therefore, we conclude that NF-κB signalling in astrocytes is not a major target for flavonoids.

Submitted by Maria Aparecida (cidazen@gmail.com) on 2017-07-31T14:17:04Z No. of bitstreams: 1 Jéssyca Wan Lume da Silva Godinho.pdf: 1739359 bytes, checksum: 0af1aff824af11b4f673e69280e7d6ec (MD5) / Made available in DSpace on 2017-07-31T14:17:04Z (GMT). No. of bitstreams: 1 Jéssyca Wan Lume da Silva Godinho.pdf: 1739359 bytes, checksum: 0af1aff824af11b4f673e69280e7d6ec (MD5) Previous issue date: 2017-05-22 / CAPES / The increasing rise in the consumption of plants and / or their products as therapeutic resources has stimulated the regulation of the use of Phytotherapy. But the offer of this therapy requires the guarantee of the access of the population to quality products, through the validation studies of the species. In this sense, the ethnobiological (ethnobotanical and ethnopharmacological) studies have provided important subsidies, which allow the investigation of the vegetal resources used therapeutically by the population. Also noteworthy are to develop chemical studies, which provide important parameters for quality control from the raw material to the final product for dispensing. Thus, this study aims at ethnopharmacological and chemical analysis of Attalea speciosa Mart. Ex Spreng. (Babaçu), because it represents a plant species of great occurrence in the state of Maranhão, widely used popularly for several therapeutic purposes, aiming at an effective contribution in the validation of the species. The ethnopharmacological approach through semi-structured interviews allowed us to verify that Attalea speciosa represents a plant species widely used in the study sample for therapeutic purposes, especially for women over 57 years of age, with the use of a fortifier being predominant. To carry out the chemical study, the mesocarp of babaçu, acquired in Arari and Esperantinópolis (Maranhão) and Fortaleza (Ceará), representing the Amazon, Cerrado and Caatinga biomes respectively, was submitted to standard extraction to obtain hydroalcoholic extracts of babassu), Followed by reactions of phytochemical characterization, through chromatographic methods and chemical reactions. Phytochemical screening confirmed the presence of phenolic compounds, saponins, condensed tannins, steroids, flavonoids and catechins. The presence of the substances rutin, myricitrin, isoquercetin, vitexin, catechin and, with emphasis, the epicatechin, were evidenced by thin layer chromatography (CCD) and high-performance liquid chromatography coupled with an ultraviolet detector (CLAE-UV-Vis). The analysis of socioeconomic data evidenced a difference between the profile pertinent to the users of plants for medicinal purposes and those of those who make therapeutic use of babassu, besides therapeutic uses of the metabolic and nutritional categories. The chemical profile revealed similarity to the extracts of the babassu mesocarp from different biomes, suggesting epicatechin as an analytical marker for the species. / A crescente ascensão no consumo de plantas e/ou seus produtos derivados como recursos terapêuticos, tem estimulado a regulamentação do uso da Fitoterapia. Mas a oferta dessa terapêutica exige a garantia do acesso da população a produtos de qualidade, através dos estudos de validação das espécies. Nesse sentido, os estudos etnodirigidos (etnobotânicos e etnofarmacológicos) têm fornecido importantes subsídios, que possibilitam a investigação dos recursos vegetais empregados terapeuticamente pela população. Destacam-se, ainda, o desenvolvimento dos estudos químicos, que fornecem parâmetros importantes para o controle de qualidade desde a matéria prima até o produto final para dispensação. Assim, este estudo objetiva realizar análise etnofarmacológica e química de Attalea speciosa Mart. ex Spreng. (babaçu), por representar espécie vegetal de grande ocorrência no estado do Maranhão, largamente empregada popularmente para diversos fins terapêuticos, visando contribuição efetiva na validação da espécie. A abordagem etnofarmacológica através de entrevistas semiestruturadas permitiu constatarmos que Attalea speciosa representa espécie vegetal amplamente empregada na amostra em estudo para fins terapêuticos, especialmente por mulheres acima de 57 anos, predominando a concordância do uso como fortificante. Para realização do estudo químico, o mesocarpo de babaçu, adquirido em Arari e Esperantinópolis (Maranhão) e em Fortaleza (Ceará), representando respectivamente os biomas Amazônia, Cerrado e Caatinga, foi submetido à extração padronizada para obtenção dos extratos hidroalcoólicos de babaçu (EHB), seguido de reações de caracterização fitoquímica, através de métodos cromatográficos e de reações químicas. No screening fitoquímico foi confirmada presença de compostos fenólicos, saponinas, taninos condensados, esteroides, flavononois e catequinas. Pela cromatografia em camada delgada (CCD) e cromatografia líquida de alta eficiência acoplada a detector de Ultravioleta (CLAE-UV-Vis) foi evidenciada a presença das substâncias rutina, miricitrina, isoquercetina, vitexina, catequina e, com destaque, a epicatequina. A análise dos dados socioeconômicos evidenciou diferença entre o perfil pertinente aos usuários de plantas para fins medicinais e o daqueles que fazem uso terapêutico do babaçu, além de usos terapêuticos das categorias metabólicas e nutricionais. O perfil químico revelou semelhança para os extratos do mesocarpo de babaçu oriundo de diferentes biomas, sugerindo epicatequina como marcador analítico para a espécie.

A Doença de Parkinson (DP) caracteriza-se por sintomas motores típicos e déficits proprioceptivos. Considerando-se o papel do estresse oxidativo na doença, o uso de agentes antioxidantes pode ter potencial terapêutico. Depois de uma revisão sobre déficits proprioceptivos na DP, esta dissertação apresenta um estudo empírico sobre o efeito da epicatequina (EC), sobre o modelo animal da 6- hidroxidopamina (6-OHDA). Ratos (n = 75) infundidos unilateralmente com 6- OHDA na via nigroestriatal receberam, após 24h, infusões intracerebrais de EC no estriado (0,031mg/mL, 0,1mg/mL, 0,31mg/mL, 1mg/mL ou veículo). O tratamento foi avaliado através dos testes de rotações induzidas por metilfenidato (40mg/kg) e apomorfina (1mg/kg), teste de motricidade sobre grade e teste da fita adesiva, além de imunoistoquímica. Os resultados mostraram que não houve diferenças entre os grupos em nenhuma das avaliações. Com base nesses resultados, concluímos que a EC, nas concentrações e condições empregadas, não foi capaz de retardar a lesão nigroestriatal ou recuperá-la. / Besides the typical motor symptoms, Parkinson´s disease (PD) is characterized by deficits in proprioception. Considering the putative role of oxidative stress in PD, antioxidants might have therapeutic value. After a review on proprioception in PD, this dissertation presents an empirical study based on the evaluation of epicatechin (EC), in 6-hydroxidopamine (6-0HDA) model of Parkinsonism. Rats (n=75) where unilaterally lesioned into the nigrostriatal pathway and treated 24h later with intracerebral infusions of EC in the striatum (0.031mg/mL, 0.1mg/mL, 0.31mg/mL, 1mg/mL or vehicle). The behavioral effects were assessed through methylphenidate (40 mg/kg) and apomorphine (1 mg/kg)-induced rotations, footfault and stick-tape tests; and brain tissue was analyzed by imunohistochemistry. There were no significant differences between groups neither in the behavioral assessments nor the histological analyses. These results showed that EC was incapable to act on either the reversal or retardation of the lesion in the nigrostriatal pathway.

A Doença de Parkinson (DP) caracteriza-se por sintomas motores típicos e déficits proprioceptivos. Considerando-se o papel do estresse oxidativo na doença, o uso de agentes antioxidantes pode ter potencial terapêutico. Depois de uma revisão sobre déficits proprioceptivos na DP, esta dissertação apresenta um estudo empírico sobre o efeito da epicatequina (EC), sobre o modelo animal da 6- hidroxidopamina (6-OHDA). Ratos (n = 75) infundidos unilateralmente com 6- OHDA na via nigroestriatal receberam, após 24h, infusões intracerebrais de EC no estriado (0,031mg/mL, 0,1mg/mL, 0,31mg/mL, 1mg/mL ou veículo). O tratamento foi avaliado através dos testes de rotações induzidas por metilfenidato (40mg/kg) e apomorfina (1mg/kg), teste de motricidade sobre grade e teste da fita adesiva, além de imunoistoquímica. Os resultados mostraram que não houve diferenças entre os grupos em nenhuma das avaliações. Com base nesses resultados, concluímos que a EC, nas concentrações e condições empregadas, não foi capaz de retardar a lesão nigroestriatal ou recuperá-la. / Besides the typical motor symptoms, Parkinson´s disease (PD) is characterized by deficits in proprioception. Considering the putative role of oxidative stress in PD, antioxidants might have therapeutic value. After a review on proprioception in PD, this dissertation presents an empirical study based on the evaluation of epicatechin (EC), in 6-hydroxidopamine (6-0HDA) model of Parkinsonism. Rats (n=75) where unilaterally lesioned into the nigrostriatal pathway and treated 24h later with intracerebral infusions of EC in the striatum (0.031mg/mL, 0.1mg/mL, 0.31mg/mL, 1mg/mL or vehicle). The behavioral effects were assessed through methylphenidate (40 mg/kg) and apomorphine (1 mg/kg)-induced rotations, footfault and stick-tape tests; and brain tissue was analyzed by imunohistochemistry. There were no significant differences between groups neither in the behavioral assessments nor the histological analyses. These results showed that EC was incapable to act on either the reversal or retardation of the lesion in the nigrostriatal pathway.

A Doença de Parkinson (DP) caracteriza-se por sintomas motores típicos e déficits proprioceptivos. Considerando-se o papel do estresse oxidativo na doença, o uso de agentes antioxidantes pode ter potencial terapêutico. Depois de uma revisão sobre déficits proprioceptivos na DP, esta dissertação apresenta um estudo empírico sobre o efeito da epicatequina (EC), sobre o modelo animal da 6- hidroxidopamina (6-OHDA). Ratos (n = 75) infundidos unilateralmente com 6- OHDA na via nigroestriatal receberam, após 24h, infusões intracerebrais de EC no estriado (0,031mg/mL, 0,1mg/mL, 0,31mg/mL, 1mg/mL ou veículo). O tratamento foi avaliado através dos testes de rotações induzidas por metilfenidato (40mg/kg) e apomorfina (1mg/kg), teste de motricidade sobre grade e teste da fita adesiva, além de imunoistoquímica. Os resultados mostraram que não houve diferenças entre os grupos em nenhuma das avaliações. Com base nesses resultados, concluímos que a EC, nas concentrações e condições empregadas, não foi capaz de retardar a lesão nigroestriatal ou recuperá-la. / Besides the typical motor symptoms, Parkinson´s disease (PD) is characterized by deficits in proprioception. Considering the putative role of oxidative stress in PD, antioxidants might have therapeutic value. After a review on proprioception in PD, this dissertation presents an empirical study based on the evaluation of epicatechin (EC), in 6-hydroxidopamine (6-0HDA) model of Parkinsonism. Rats (n=75) where unilaterally lesioned into the nigrostriatal pathway and treated 24h later with intracerebral infusions of EC in the striatum (0.031mg/mL, 0.1mg/mL, 0.31mg/mL, 1mg/mL or vehicle). The behavioral effects were assessed through methylphenidate (40 mg/kg) and apomorphine (1 mg/kg)-induced rotations, footfault and stick-tape tests; and brain tissue was analyzed by imunohistochemistry. There were no significant differences between groups neither in the behavioral assessments nor the histological analyses. These results showed that EC was incapable to act on either the reversal or retardation of the lesion in the nigrostriatal pathway.

Thesis (Ph. D.)--Pennsylvania State University, 1982. / Includes bibliographical references.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Dominika Sobolová Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Pharmacokinetics of flavanols This work is focusing on summarizing available information about the fate of flavanols in the organism. It is necessary to know the pharmacokinetics to explain their biological effects. In contrast to other flavonoids, they occur in the form of aglycones in plant foods. Galoylation, polymerization and optical isomerism have an important influence on the pharmacokinetics. Partial absorption of monomers begins in the small intestine after oral ingestion. In addition to the liver, the extensive metabolic changes take place even in the enterocytes. The resulting metabolites enter the circulation or they are effluxed back into the intestinal lumen, especially in the case of (epi)catechin sulfates. Epicatechin and catechin are present almost exclusively as glucuronides, sulfates or methylated compounds in the plasma. On the contrary, free unconjugated forms prevail within the gallates. The extent of their absorption is lower. They are excreted via biliary excretion, while other catechins are quickly eliminated by the kidneys in urine. The bioavailability of the parent...