Made available in DSpace on 2015-05-14T12:59:59Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2254071 bytes, checksum: 5ef1f814625ed46426cc35ec211b8399 (MD5) Previous issue date: 2013-03-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Root bark infusions of the plant Cissampelos sympodialis Eichl (Menispermaceae) are used in folk medicine, in Northeast Brazil, for the treatment of diseases of the respiratory and digestive tracts. Previous studies showed that the hydroalcoholic extract of the leaves (AFL) of the plant and warifteine (W), alkaloid bisbenzylisoquinolinic, presented anti-inflammatory and anti-allergic effects. This study evaluated the effect of the oral treatment of mice with W and methyl warifteine (MW) in the paw edema formation induced by phlogistic agents, vascular leakage and cell migration in acute inflammatory models and the effect of oral treatment with AFL and its alkaloids (W and MW) in chronic inflammation represented by the experimental model of food allergy (BALB / c mice sensitized with ovalbumin - OVA). Oral treatment with W reduced the paw edema induced by carrageenan, histamine and prostaglandin E2, an effect not presented in MW treatment. The warifteine and methyl-warifteine also reduced the vascular leakage, however without inhibiting cell migration associated with inflammation. In the experimental model of food allergy the treatment with W induced weight gain in animals with decreased of diarrhea. Methylation of warifteine did not induce weight gain nor inhibited allergic diarrhea during the allergen challenge. However treatment with AFL did not induce weight gain nor inhibited allergic diarrhea. In contrast, treatment with the AFL or its alkaloids reduced the IgE specific for ovalbumin (OVA) titer, increased the proportion of CD4 + or CD8+ T lymphocytes in mesenteric lymph nodes. The proportion of regulatory T lymphocytes in the mesenteric lymph nodes was also increased by the treatments. In vitro experiments, with cells from mesenteric lymph nodes of sensitized animals, demonstrated that W and MW inhibited the secretion of interleukin (IL-) 12 and IL-10 with no change in the interferon-γ (IFN-γ) and IL- 13 levels. These results demonstrated that the oral treatment with warifteine presented anti-inflammatory activity by inhibiting the action of mediators of inflammation and the methylation of the molecule did not improve this effect. Also, the treatment with AFL, W and MW showed immunomodulatory effects in food allergy with increased of Treg cells and decreased of cytokines derived from cells of the innate immune mechanism independent of that of the adaptive immune mechanism. / Infusões das raízes da planta Cissampelos sympodialis Eichl (Menispermaceae) são utilizadas, pela medicina popular, no Nordeste Brasileiro, para o tratamento de doenças do trato respiratório e digestório. Estudos prévios demonstram que o extrato hidroalcoólico das folhas (AFL) da planta e a warifteina (W), alcaloide bisbenzilisoquinolínico, apresentam efeitos anti-inflamatórios e antialérgicos. Esse estudo avaliou, portanto, o efeito do tratamento oral de camundongos com W e a metil-warifteina (MW) na formação do edema de pata induzido por agentes flogísticos, no extravasamento vascular e na migração celular em modelos de inflamação aguda e o efeito do tratamento oral com a AFL e seus alcaloides (W e MW) na inflamação crônica representada pelo modelo experimental de alergia alimentar (camundongos BALB/c sensibilizados com ovalbumina - OVA). O tratamento com a W reduziu o edema de pata induzido por carragenina, por histamina ou prostaglandina E2, efeito esse não observado com o tratamento com MW. A warifteina e a metil-warifteina também reduziram o extravasamento vascular, contudo sem inibir a migração celular associada à inflamação. No modelo experimental de alergia alimentar o tratamento com W induziu ganho de peso dos animais com diminuição da diarreia. A metilação da warifteina, embora não tenha induzido o ganho de peso diminuiu a diarreia durante os desafios com o alérgeno. Todavia o tratamento com AFL não induziu o ganho de peso e nem inibiu a diarreia alérgica. Diferentemente, os tratamentos com o AFL e com os alcaloides reduziram os títulos de IgE específica para ovalbumina (OVA), aumentaram a proporção de linfócitos T CD4+ e CD8+ no linfonodo mesentérico. A proporção de linfócitos T reguladores foi aumentada no linfonodo mesentérico pelos tratamentos em estudo. Os experimentos in vitro, com células do linfonodo mesentérico de animais sensibilizados, demonstraram que W e MW inibiram a secreção de interleucina (IL-)12 e IL-10, sem alteração nos níveis de interferon-γ (IFN-γ) e IL-13. Esses resultados demonstraram que o tratamento oral com warifteina apresentou atividade anti-inflamatória por inibir a ação de mediadores da inflamação e que a metilação da molécula não potencializou seu efeito. Também, os tratamentos com AFL, W e MW apresentaram efeitos imunomoduladores na alergia alimentar com aumento de células Treg e com diminuição de citocinas oriundas de células do mecanismo imune inato independente das do mecanismo imune adaptativo.

Menispermaceae é uma família de distribuição pantropical que compreende diversos hábitos, em sua maioria, trepadeiras herbáceas e lianas, além de ervas, arbustos e árvores e onde se faz presente a variação cambial do tipo câmbios sucessivos. Este trabalho apresenta um estudo anatômico do caule e da raiz com ênfase nas lianas e trepadeiras herbáceas. Estudou-se 10 gêneros, 14 espécies e 31 espécimes. Cinco espécies são trepadeiras herbáceas, uma é herbácea (Cissampelos ovalifolia), uma é arbustiva (Abuta grandifolia), e o restante são lianas. As lianas e o arbusto apresentam em seus caules, a variação cambial do tipo câmbios sucessivos, enquanto as trepadeiras herbáceas e a erva não apresentam essa variação estrutural. Demonstra-se na liana Abuta imene, de maneira inédita para a família, que o periciclo origina o tecido conjuntivo, e esse, por sua vez, os câmbios sucessivos. Na análise comparativa do xilema secundário em diversos anéis sucessivos contidos no mesmo caule, destaca-se que o lenho produzido pelos novos anéis vasculares, normalmente, não difere qualitativamente do anel vascular original, no entanto há diferenças quando aos caracteres quantitativos: os diâmetros dos elementos de vasos sofreram aumento estatisticamente significativo no sentido centro-periferia. A análise do caule entre dois hábitos de Abuta grandifolia (liana X arbusto) mostrou que ambos possuem o mesmo padrão anatômico, porém, destaca-se que os diâmetros de elementos de vasos são menores no arbusto. Variações quantitativas ocorrem entre o lenho de caule e a raiz de trepaderias herbáceas e estão relacionadas ao diâmetro e comprimento dos elementos de vasos que são maiores nos caules. Alguns dados são relatados, pela primeira vez, para essa família: (1) Classifica-se o sistema subterrâneo de Disciphania hernandia como raiz tuberosa; (2) Ruptura do raio vascular através da transformação de iniciais radiais em iniciais fusiformes no xilema e floema; (3) A constatação de câmbios sucessivos na raiz da liana Chondrodendron platiphyllum. Apesar da similaridade quanto à estrutura anatômica geral do caule, existem caracteres que separam as trepadeiras herbáceas das lianas, tais como: o tipo de parênquima, morfologia dos cristais, o diâmetro e a distribuição dos elementos de tubos crivados e a transformação das iniciais, tanto fusiformes quanto radiais nas trepadeiras herbáceas. Fornece-se, ainda, alguns aspectos anatômicos do floema secundário no caule. Recomenda-se a padronização de estudos do lenho na família através do primeiro anel. Discute-se a presença de raio medular na família. Conclui-se que os caules das lianas são muito similares, portanto, a identificação das porções do lenho utilizadas em objetos comercializados somente é possível ao nível de família. / The pantropical family Menispermaceae includes several habits, like herbaceous vines, herbs, shrubs, and trees, showing cambial variant of successive type. The present study is an anatomical approach of stem and root of woody and herbaceous vine habits. In the present study, 31 specimens were investigated, sampling 10 genera and 14 species. Of those species, five are herbaceous vines, one is herb (Cissampelos ovalifolia) and one is shrub (Abuta grandifolia), and the rest are woody vines. Stems of woody vines and shrubs show successive cambia, not assigned to herbs and herbaceous vines. For the first time in the family, it is observed in the woody vine Abuta imene that the conjunctive tissue originates from the pericycle, and that the successive cambia, on its turn, originates from the conjunctive tissue. In the comparative analysis of secondary xylem in its several successive rings in the same stem, the wood produced by new vascular rings does not differ qualitatively from the original vascular ring, while there are differences in quantitative characters: diameter of vessel elements show significant increase in centreperiphery direction. The stem analysis between two habits of Abuta grandifolia (woody vine X shrub) shows that both have the same anatomical pattern. However, diameter of vessel elements is smaller in shrubs. Quantitative variation occurs between stem and root in herbaceous vine wood, and are related to diameter and length of vessel elements, which are larger in stems. Some data are described for the family for the first time: (1) The subterranean system of Disciphania hernandia is assigned as root tuber; (2) Splitting of ray by transformation of ray initials to fusiform initials in xylem and phloem; (3) Presence of successive cambia in woody vine root of Chondrodendron platiphyllum. Despite the anatomical general resemblance of stem, there are characters that distinguish herbaceous from woody vines, like: the kind of parenchyma, crystal morphology, diameter and distribution of sieve tube elements, and transformation of fusiform and ray initials in herbaceous vines. Additionally, some anatomical aspects of secondary phloem in stem are shown. The standardization of woody studies in the family considering the first ring is recommended. Discussions are made about the presence of medullary ray in the family. It is concluded that the stem of woody vines are very similar to each other, and thus, identification of woody portions used in commercialized objects is possible only at familial level.

Le paludisme, la maladie la plus dévastatrice des régions tropicales fait l’objet de nombreuses recherches ayant pour but de trouver des médicaments préventifs, du matériel de protection, de nouveaux traitements, des vaccins, …<p>Notre travail s’est inscrit dans la recherche des composés naturels actifs sur l’agent pathogène, le Plasmodium. Nos investigations phytochimiques et pharmacologiques ont porté sur Triclisia sacleuxii, une plante utilisée en médecine traditionnelle pour traiter diverses maladies dont deux parasitaires: la schistosomiase et l’ascardiose. Elle est aussi employée dans la préparation du poison de flèche. De plus, T. sacleuxii appartient à la famille des Menispermaceae, une famille riche en alcaloïdes bisbenzylisoquinoléiques (BBIQ). Ces composés ont de nombreuses propriétés biologiques dont l’activité antipaludique et trypanocide. Plusieurs autres espèces appartenant au genre Triclisia sont utilisées en médecine traditionnelle pour traiter la fièvre, le paludisme et d’autres pathologies. Ces éléments ont motivé la recherche dans cette plante des composés à activité antiplasmodiale. En effet, la plupart des composés que nous en avons isolés (p 12) sont actifs aussi bien sur la souche chloroquino-sensible (3D7) que sur la souche chloroquino-résistante (W2) que nous avons testées.<p>Deux d’entre eux ont en plus une activité plus élevée vis-à-vis de la souche choroquino-résistante.<p>Les composés actifs sur Plasmodium falciparum ont également montré une toxicité à l’égard de Trypanosoma brucei brucei, une sous-espèce apparentée à celles qui sont à la base de la maladie du sommeil en Afrique Centrale et de l’Est.<p>A part les usages mentionnés précédemment, T. sacleuxii est en plus employée comme antidote contre les morsures de serpents. Ce qui voudrait dire qu’elle pourrait renfermer des inhibiteurs d’enzymes.<p>Aussi, des BBIQ ont déjà démontré une activité inhibitrice de l’acétylcholinéstérase (AChE) et des phospholipases A2. Sur base de ces informations, nous avons assigné un troisième objectif à notre investigation qui cible l’AChE en correlation avec la maladie d’Alzheimer (MA). La MA est une pathologie neurodégénérative qui affecte en général les personnes âgées de plus de 60 ans, caractérisée entre autres par une perte progressive de la mémoire, une détérioration de plusieurs fonctions cognitives, de troubles neurologiques et du comportement, … Les différents extraits alcaloïdiques ont montré un degré d’inhibition de l’AChE élevé ( 80 - 90%) à une concentration de 100 μg/ml. Avec les composés purs, l’inhibition est très variable (30 - 90 %) suivant la structure. Enfin, nous avons effectué des investigations pour déterminer le mode d’action antiplasmodiale des BBIQ majeurs isolés de T. sacleuxii. Il apparaît que non seulement toutes les BBIQ n’agissent pas par un même mode d’action, mais aussi un même composé pourrait agir simultanément suivant deux ou plusieurs mécanismes différents.<p><p><p>Malaria, the most devastating disease in tropical areas, is currently a target of numerous researches, aiming to find preventive medicines, protective tools, new treatments and vaccines. In a search for antiplasmodial natural compounds, we have undertaken phytochemical and pharmacological investigations on Triclisia sacleuxii, used in traditional medicine to treat various ailments including two parasitological diseases; schistosomiasis and ascariasis. It is also used as an arrow poison.<p>Triclisia sacleuxii belongs to the Menispermaceae family, which is known to contain bisbenzylisoquinolines. These components have shown various biological activities among which antimalarial and trypanocidal activity. Furthermore, many Triclisia species are used in traditional medicine for treating fever and malaria along with other disorders.<p>With this background the research was set out to investigate on possible antiparasitic compounds active against Plasmodium falciparum.<p>Most of the compounds isolated in this work were active towards both chloroquine sensitive strain (3D7) and chloroquine resistant Plasmodium strain (W2). Interestingly some of them demonstrated selectivity for the resistant strain.<p>The compounds which displayed antiplasmodial activity also showed toxicity against Trypanosoma brucei brucei, a parasite related to those which cause sleeping sickness.<p>Besides Triclisia sacleuxii traditional uses mentioned above, it is also used as a snakebites antidote. This suggests that it might contain enzymes inhibitors. Additionally, in previous works, bisbenzylisoquinolines which are believed to be present in T. sacleuxii, have displayed phospholipases A2 and acetylcholinesterase inhibitory activity. On the basis of these informations, the third aim of our investigation targeted acetylcholinesterase (AChE), an enzyme involved in Alzheimer’s disease (AD). AD is a neurodegenerative disease occurring mostly in people aged beyond 60 years, characterised by a progressive loss of memory, impairement of multiple cognitive functions, neurological and behavior disorders, Our results have demonstrated that leaves, stems and roots alkaloidal fractions have high anti-AChE activity. Pure compounds exhibited a structure-dependent activity ranging from 30 up to 90% at a concentration of 100μg/ml).<p>Finally, we have undertaken an investigation on the antiplasmodial mode of action of the major alkaloids. It appears that not only the BBIQ do not act by a same mechanism, but also a single compound may act by more than one mode of action. / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished