SOUZA, J. S. N. Contribuição ao Estudo Químico de Espécies do Estado do Ceará: Heliotropium indicum Linn, Heliotropium polyphyllum Lehm e Ganoderma lucidum. 2009. 250 f. Tese (Doutorado em Química) - Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2009. / Submitted by Daniel Eduardo Alencar da Silva (dealencar.silva@gmail.com) on 2014-11-17T17:51:57Z No. of bitstreams: 1 2009_tese_jsnsouza.pdf: 11597625 bytes, checksum: 84b35a64cbb3529396dbc1b642b46d88 (MD5) / Approved for entry into archive by José Jairo Viana de Sousa(jairo@ufc.br) on 2016-03-18T23:44:30Z (GMT) No. of bitstreams: 1 2009_tese_jsnsouza.pdf: 11597625 bytes, checksum: 84b35a64cbb3529396dbc1b642b46d88 (MD5) / Made available in DSpace on 2016-03-18T23:44:30Z (GMT). No. of bitstreams: 1 2009_tese_jsnsouza.pdf: 11597625 bytes, checksum: 84b35a64cbb3529396dbc1b642b46d88 (MD5) Previous issue date: 2009 / This work reports the phytochemistry study of two species of the genus Heliotropium: H. indicum Linn and H. polyphyllum Lehm, and of the macrofungal Ganoderma lucidum, collected in the State of Ceará. The analysis of the essential oils from aerial parts’ of the species of Heliotropium, for different extraction techniques, allowed the identification of different secondary metabolic, from hydrocarbons, terpenoids, alcohols even sesquiterpenoids. For the essential oil from roots OEHI all 17 constituents chemicalents were identified and the fitol (49,10%) were the major compound. The phytochemistry investigation from etanolic extract of the roots of H. indicum resulted in the isolation, among others compounds, one pirrolizidine alkaloid that has been named as helindicine (HI-2). The phytochemistry study from extract etanolic for aerial parts’ of H. polyphyllum allowed the isolation of the alkaloid licopsamine (HP-1). The chromatographic analysis of the fixed constituints from etanolic extract of Ganoderma lucidum allowed the isolation of the steroids ergostane: ergosta-7,22,-dien-3-one, ergosta-22-en-3,4,8-triol, ergosta-1,4,8(14),22-tetraen-3-one, and the mixture of ergosta-5,9,22-trien-3-ol and ergosta-5,22-dien-3-ol. A series of derived from steroid ergosta-7,22-dien-3-one was developed starting from the modification in the carbon C-3 with obtaining of alcohols, steres (formil and acetil) and oxima. The structural determination of all natural products, and derived was performed by mean of spectroscopic techniques such MS, IR, 1H and 13C NMR, including uni and bi-dimensional pulse sequences. The identification of the volatile constitution was performed by GC/MS for the qualitative analysis while GC/FID was used for the quantitative analysis, and still comparison to data published in the literature was also used for identification wherever the case. / Este trabalho relata o estudo fitoquímico de duas espécies do gênero Heliotropium: H. indicum Linn e H. polyphyllum Lehm e do macrofungo Ganoderma lucidum, coletados no Estado do Ceará. A análise dos óleos essenciais das partes aéreas das espécies de Heliotropium, por diferentes técnicas de extração, permitiu a identificação de diferentes metabólitos secundários, desde hidrocarbonetos, terpenóides, álcoois até sesquiterpenóides. No óleo essencial das raízes OEHI, foram identificados 17 constituintes químicos, sendo o fitol (49,10%) o composto majoritário. A investigação fitoquímica do extrato etanólico das raízes de H. indicum resultou no isolamento, entre outros compostos, um alcalóide pirrolizidínico denominado helindicina (HI-2). O estudo fitoquímico do extrato etanólico das partes aéreas de H. polyphyllum permitiu o isolamento do alcalóide licopsamina (HP-1). A análise cromatográfica dos constituintes fixos do extrato etanólico de Ganoderma lucidum permitiu o isolamento dos esteróides ergostanos: ergosta-7,22,-dien-3-ona, ergosta-22-en-3,4,8-triol, ergosta-1,4,8(14),22-tetraen-3-ona e a mistura de ergosta-5,9,22-trien-3-ol e ergosta-5,22-dien-3-ol. Uma série de derivados do esteróide ergosta-7,22-dien-3-ona foi desenvolvida a partir da modificação no carbono C-3 com obtenção de álcoois, ésteres (formil e acetil) e oxima. A determinação estrutural dos contituintes não voláteis e derivados foi realizada através de métodos espectroscópicos EM, IV e RMN 1H e 13C, incluindo sequencias de pulso uni e bi-dimensionais. A identificação dos constituintes voláteis foi desenvolvida por cromatografia gasosa acoplada à espectrometria de massas (CG/EM) para análise qualitativa, enquanto (CG/DIC) para análise quantitativa e ainda comparação com dados descritos na literatura.

Common heliotrope (Heliotropium europaeum L.) is an herbaceous Mediterranean summer annual that grows on areas devoid of vegetation in the dry-land cropping region located in the north-west of the state of Victoria, Australia. This region is known as the Mallee, and common heliotrope is considered a weed here because it transpires soil water that could otherwise be used by ensuing crops, and is toxic to livestock. / In this study, laboratory experiments have shown that germination of seeds of common heliotrope is not limited by light, cold treatment, or a leacheable inhibitor. Temperature and water potential (and perhaps depth inhibition) are the principal environmental factors that limit germination. Although 100 % of seeds will germinate under optimal conditions, these conditions are rarely met in the field, and the percentage of seeds that germinate at sub-optimal conditions changes seasonally and between Australian populations. This is the principal mechanism of dormancy in the species, ensuring that seeds do not germinate when conditions are unfavourable for continued growth and that in the field, germination of a seed population is fractional, spreading risk temporally. Germination of seeds of common heliotrope does not conform to the assumptions of the hydrothermal time model frequently used to predict field emergence of weed species. / Field observations and simulated rainfall experiments on a consistent soil type (Calcarosol with a clay loam surface texture and clay subsoil) indicated that approximately 20 mm of rainfall is the minimum amount required for germination and emergence of common heliotrope. Field experiments using lysimeters indicated that this is also the amount required for minimal reproduction on the same soil type. Although common heliotrope can successfully reproduce upon the rainfall event which causes its germination, its growth is indeterminate, and further access to moisture will result in massively increased reproductive output. Plants will continue to grow and produce seed over summer until they are killed by drought or senesce in autumn. Laboratory and field studies showed that root growth in common heliotrope is relatively slow, and is opportunistic in areas where moisture becomes available. / Simulation of soil water and temperature fluxes showed that soil type has a large impact on the amount and duration of water potential that seeds and plants are exposed to. In the case of common heliotrope, this is critical in determining regional prevalence and distribution in the north-west of Victoria. It is recommended that studies of arid species reliant on isolated rainfall events for emergence should consider absolute water availability and not in terms of rainfall amount alone. / Analysis of long term summer rainfall data from the Victorian Mallee indicates that there is potential for reducing the cost of controlling common heliotrope by using residual pre-emergent sulfonylurea or triazine herbicides, instead of the traditional post-emergent herbicides or cultivation. More information is needed on the efficacy of such residual herbicides on common heliotrope and other summer weeds, and their impact on subsequent crops before the full potential of this management option is known. Reduced cost of control could also be achieved by economic analysis of the likely benefits of controlling each emerging cohort of common heliotrope, and a framework for decision making is suggested.

FundaÃÃo de Amparo à Pesquisa do Estado do Cearà / CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Este trabalho relata o estudo fitoquÃmico de duas espÃcies do gÃnero Heliotropium: H. indicum Linn e H. polyphyllum Lehm e do macrofungo Ganoderma lucidum, coletados no Estado do CearÃ. A anÃlise dos Ãleos essenciais das partes aÃreas das espÃcies de Heliotropium, por diferentes tÃcnicas de extraÃÃo, permitiu a identificaÃÃo de diferentes metabÃlitos secundÃrios, desde hidrocarbonetos, terpenÃides, Ãlcoois atà sesquiterpenÃides. No Ãleo essencial das raÃzes OEHI, foram identificados 17 constituintes quÃmicos, sendo o fitol (49,10%) o composto majoritÃrio. A investigaÃÃo fitoquÃmica do extrato etanÃlico das raÃzes de H. indicum resultou no isolamento, entre outros compostos, um alcalÃide pirrolizidÃnico denominado helindicina (HI-2). O estudo fitoquÃmico do extrato etanÃlico das partes aÃreas de H. polyphyllum permitiu o isolamento do alcalÃide licopsamina (HP-1). A anÃlise cromatogrÃfica dos constituintes fixos do extrato etanÃlico de Ganoderma lucidum permitiu o isolamento dos esterÃides ergostanos: ergosta-7,22,-dien-3-ona, ergosta-22-en-3,4,8-triol, ergosta-1,4,8(14),22-tetraen-3-ona e a mistura de ergosta-5,9,22-trien-3-ol e ergosta-5,22-dien-3-ol. Uma sÃrie de derivados do esterÃide ergosta-7,22-dien-3-ona foi desenvolvida a partir da modificaÃÃo no carbono C-3 com obtenÃÃo de Ãlcoois, Ãsteres (formil e acetil) e oxima. A determinaÃÃo estrutural dos contituintes nÃo volÃteis e derivados foi realizada atravÃs de mÃtodos espectroscÃpicos EM, IV e RMN 1H e 13C, incluindo sequencias de pulso uni e bi-dimensionais. A identificaÃÃo dos constituintes volÃteis foi desenvolvida por cromatografia gasosa acoplada à espectrometria de massas (CG/EM) para anÃlise qualitativa, enquanto (CG/DIC) para anÃlise quantitativa e ainda comparaÃÃo com dados descritos na literatura. / This work reports the phytochemistry study of two species of the genus Heliotropium: H. indicum Linn and H. polyphyllum Lehm, and of the macrofungal Ganoderma lucidum, collected in the State of CearÃ. The analysis of the essential oils from aerial partsâ of the species of Heliotropium, for different extraction techniques, allowed the identification of different secondary metabolic, from hydrocarbons, terpenoids, alcohols even sesquiterpenoids. For the essential oil from roots OEHI all 17 constituents chemicalents were identified and the fitol (49,10%) were the major compound. The phytochemistry investigation from etanolic extract of the roots of H. indicum resulted in the isolation, among others compounds, one pirrolizidine alkaloid that has been named as helindicine (HI-2). The phytochemistry study from extract etanolic for aerial partsâ of H. polyphyllum allowed the isolation of the alkaloid licopsamine (HP-1). The chromatographic analysis of the fixed constituints from etanolic extract of Ganoderma lucidum allowed the isolation of the steroids ergostane: ergosta-7,22,-dien-3-one, ergosta-22-en-3,4,8-triol, ergosta-1,4,8(14),22-tetraen-3-one, and the mixture of ergosta-5,9,22-trien-3-ol and ergosta-5,22-dien-3-ol. A series of derived from steroid ergosta-7,22-dien-3-one was developed starting from the modification in the carbon C-3 with obtaining of alcohols, steres (formil and acetil) and oxima. The structural determination of all natural products, and derived was performed by mean of spectroscopic techniques such MS, IR, 1H and 13C NMR, including uni and bi-dimensional pulse sequences. The identification of the volatile constitution was performed by GC/MS for the qualitative analysis while GC/FID was used for the quantitative analysis, and still comparison to data published in the literature was also used for identification wherever the case.

Submitted by Cleide Dantas (cleidedantas@ufpa.br) on 2014-05-27T13:52:50Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_EstudosPreformulacaoFormulacao.pdf: 1891835 bytes, checksum: 30e822bccdb4ea2da7abab6187ae1418 (MD5) / Approved for entry into archive by Ana Rosa Silva (arosa@ufpa.br) on 2014-09-08T17:32:24Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_EstudosPreformulacaoFormulacao.pdf: 1891835 bytes, checksum: 30e822bccdb4ea2da7abab6187ae1418 (MD5) / Made available in DSpace on 2014-09-08T17:32:24Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_EstudosPreformulacaoFormulacao.pdf: 1891835 bytes, checksum: 30e822bccdb4ea2da7abab6187ae1418 (MD5) Previous issue date: 2010 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Heliotropium indicum L. (Boraginaceae) é um subarbusto que atinge até 70 cm de altura, é amplamente distribuído geograficamente. A espécie é conhecida como fedegoso na região norte e nordeste. Diante do potencial biológico desta espécie este trabalho objetiva determinar parâmetros de qualidade da droga vegetal até o produto final e avaliar a atividade antimicrobiana de suas folhas, com finalidade de se obter uma formulação fitoterápica semi-sólida. Para isso utilizou-se parâmetros de controle de qualidade físico, químico e físico-químico descritos na Farmacopéia Brasileira e literatura pertinente. A droga vegetal foi classificada como pó grosso, apresentou valores médios de perda por dessecação e cinzas totais de 12,88% e 17,14%, respectivamente. A análise termogravimétrica do pó e do extrato liofilizado mostrou que ambos apresentaram boa estabilidade térmica até 180°C. Os espectros na região do IV mostraram um aumento na intensidade das bandas de absorção do extrato liofilizado, que pode está relacionado à extração dos constituintes químicos da matriz celular. A prospecção química do extrato confirmou a presença de classes de metabólitos secundários já relatados em literatura. A fração clorofórmica sugere a presença de alcalóides pelo teste de precipitação com reagente de Dragendorff. A CCD e a CLAE mostraram uma possível presença de uma mesma substância nas frações alcaloídicas e hexânicas. O extrato bruto de H. indicum L. inibiu o crescimento de Staphylococcus aureus apresentando halos de 12,5 mm±0,707 e 10,5 mm±0,707 para as concentrações de 500 mg/mL e 250 mg/mL, respectivamente. As misturas físicas do extrato com os adjuvantes farmacêuticos, utilizados no desenvolvimento da formulação fitoterápica, não apresentaram incompatibilidade física e não houve modificações significativas no perfil de absorção entre os compostos analisados. A formulação fitoterápica semi-sólida manteve-se estável após sua preparação, após a submissão do gel a força centrípeta e após ação do estresse térmico. / Heliotropium indicum L. (Boraginaceae) is a shrub, reaches up to 70 cm high. It is known as “fedegoso” in the north and northeast of Brazil. Because of the biological potential of this species, this work aims to determine the quality parameters of the vegetable drug to the final product and evaluate the antimicrobial activity of the leaves of H. indicum L. The purpose of obtaining a phytotherapic formulation semisolid, we used the parameters of quality control physical, chemical and physicalchemical described in the Brazilian Pharmacopoeia and others literature. The vegetable drug was classified as coarse powder, showed values of loss on drying and total ash of 12.88% and 17.14%, respectively. The thermogravimetric analysis of the powder and the extract showed that both had good physical stability up to 180 °C. The spectra in the region IR showed an increase in the intensity of the absorption bands of the extract, which may relates to the extraction of chemical constituents of the cellular matrix. The prospecting chemical extract confirmed the presence of classes of secondary metabolites already reported in literature. The chloroform fraction suggests the presence of alkaloids by precipitation test with Dragendorff reagent. The TLC and HPLC showed a possible presence of the same substance in the alkaloidal and hexane fractions. The crude extract inhibited the growth of Staphylococcus aureus with halos of 12.5 mm ± 0.707 and 10.5 ± 0.707 mm for concentrations of 500 and 250 mg / mL, respectively. The physical mixtures of the extract with adjuvant pharmaceutical used to develop the phytotherapic formulation showed no physical incompatibility and no significant changes in the absorption profile of the compounds analyzed. The phytotherapic formulation semi-solid has a good stability after the preparation, after the submission of the gel by centripetal force and after the action of heat stress.

La ciguatéra, ichtyosarcotoxisme majoritairement rencontré dans la zone intertropicale, trouve son origine dans la consommation de poissons tropicaux contaminés par des neurotoxines marines, les ciguatoxines (CTXs). Ces polyéthers polycycliques synthétisés par les micro-algues du genre Gambierdiscus, se fixent de façon privilégiée aux canaux sodiques dépendant du potentiel. Cependant, ce seul mode d'action n'explique pas tous les symptômes observés dans la ciguatéra notamment les manifestations particulières de type inflammatoire. L'effet de deux toxines ciguatérigènes, la P-CTX-1B et la P-CTX-3C, ainsi que l'activité d'un analogue, la brévétoxine PbTx-3, sur la modulation des médiateurs de l'inflammation que sont les cytokines, a été caractérisé sur un modèle d'étude in vitro de cellules de macrophages murins RAW 264.7. Le suivi de l'expression génique au moyen de techniques de PCR quantitative a révélé que la P-CTX-1B est capable d'induire les cytokines pro-inflammatoires interleukine (IL)-1β, IL-6 et le Tumor Necrosis Factor (TNF)-α, et l'anti-inflammatoire IL-10. Par ailleurs, alors que les traitements proposés par la médecine occidentale sont essentiellement symptomatiques, la médecine traditionnelle propose l'utilisation de nombreuses plantes dont certaines sont capables de réduire les effets des CTXs in vitro et in vivo. La nécessité d'enrichir l'arsenal thérapeutique de la ciguatéra ainsi que l'implication probable des mécanismes inflammatoires dans cette pathologie nous ont conduits à caractériser le potentiel anti-inflammatoire de quatre plantes parmi celles traditionnellement employées dans le Pacifique. Les effets d'extraits aqueux de Cerbera manghas, Euphorbia hirta, Heliotropium foertherianum et Vitex trifolia sur la cinétique de synthèse des ARNm ainsi que sur la production des protéines cytokiniques, ont été étudiés sur le modèle d'induction de macrophages murins stimulés par un lipopolysaccharide bactérien (LPS). Les résultats montrent que E. hirta et V. trifolia possèdent les activités anti-inflammatoires les plus intéressantes et cette dernière a été sélectionnée pour de plus amples tests. L'extrait aqueux de V. trifolia montre la capacité à inhiber les cytokines pro-inflammatoires IL-1β, IL-6 et TNF-α et à induire l'anti-inflammatoire IL-10 dépendant du LPS. La finalité du projet doit permettre l'étude de principes actifs isolés des plantes sélectionnées et les composés d'intérêt pourront être testés sur modèle animal avant d'être validés sur l'homme. Ainsi de nouveaux traitements thérapeutiques de la ciguatéra pourront-ils être proposés. Mots clés : ciguatéra, ciguatoxine, cytokine, PCR quantitative, ELISA, physiopathologie, remèdes traditionnels, Vitex trifolia, Euphorbia hirta, Cerbera manghas, Heliotropium foertherianum.

La ciguatéra est une intoxication liée à l'ingestion de poissons de récif corallien devenus toxiques par l'accumulation d'une ou plusieurs neurotoxines d'origine dinoflagellaire. Cet ichtyosarcotoxisme représente une des plus fréquentes formes d'intoxication dans les régions tropicales et subtropicales et se manifeste par une cohorte de symptômes complexes chez l'homme. La première partie de cette étude a consisté à mettre en évidence l'action de la CTX-1B du Pacifique (P-CTX-1B) sur la surproduction d'oxyde nitrique (NO) via la modulation de son enzyme de synthèse, la NO synthétase inductible (iNOS), impliquant ainsi pour la première fois ce mécanisme pathogénique inflammatoire dans la ciguatéra. La deuxième partie concerne les travaux de l'évaluation de potentiel thérapeutique d'une trentaine d'extraits de plantes. En effet, la médecine occidentale reste peu efficace et symptomatique pour traiter durablement les patients souffrant de ciguatéra. La troisième partie décrit la sélection de trois de ces plantes et les études phytochimiques menées. Ces travaux ont conduit à l'identification de trois molécules : la quercitrine, l'acide rosmarinique et l'agnuside. Cette thèse a abouti au dépôt d'un brevet sur l'activité détoxifiante de l'acide rosmarinique.