For over a century, documented scientific research and debate has revolved around the therapeutic properties of the medicinal plant Echinacea angustifolia. With overwhelming evidence demonstrating the biological activity of its root phytochemical constituents, the genetic improvement of E. angustifolia by selecting phytochemically rich genotypes has garnered both scientific and commercial interest. This dissertation presents results of multi-disciplinary experiments intended to help establish scientifically based guidelines for breeding efforts aimed at developing therapeutically superior varieties of E. angustifolia in British Columbia. Cultivated E. angustifolia populations from British Columbia and Washington were grown in a common greenhouse environment to identify possible genetically superior populations with respect to root concentrations of therapeutically relevant caffeic acid derivatives (CAD) and alkamides. However, none of the studied cultivated E. angustifolia populations showed significant genetic differences in terms of root phytochemical traits. In the second part, an investigation into correlations between root and shoot phytochemical concentrations in field- and greenhouse-grown plants revealed that concentrations of therapeutically relevant marker compounds in shoots were generally poor predictors of concentrations in roots. Some weak yet significant positive correlations were observed between root and shoot concentrations of CADs but were inconsistent between the two environments. Significant genotype by environment interactions were documented for the first time in phytochemical traits of E. angustifolia in a study of five genetically homogeneous populations grown in three different environments, including 1 greenhouse and 2 field sites in British Columbia. For the final objective, in vitro bioassays showed that environmentally and genotypically related differences in concentrations of CADs and alkamides in E. angustifolia ethanolic root extracts did not translate into significant differences in their anti-inflammatory potential as measured by pro-inflammatory interleukin (IL-6 and IL-8) secretion in human bronchial epithelial (BEAS-2B) cells challenged with rhinovirus. When used in isolation however, pure tetraene alkamide showed a significant inhibitory effect on secretion, thereby further supporting the use of high alkamide production as a selection criterion for therapeutic E. angustifolia cultivar development. A series of recommendations derived from these findings are presented along with ideas for important future studies in the field of Echinacea research.

Submitted by DAYANE GRAZIELLA PEREIRA DE O. DOS SANTOS null (daygrazi@hotmail.com) on 2016-05-23T04:00:20Z No. of bitstreams: 1 Dayane pdf.pdf: 1015868 bytes, checksum: 6aca3f66299016c2bab0b0b8f46c4cb4 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-05-25T17:15:55Z (GMT) No. of bitstreams: 1 santos_dgpo_me_bot.pdf: 1015868 bytes, checksum: 6aca3f66299016c2bab0b0b8f46c4cb4 (MD5) / Made available in DSpace on 2016-05-25T17:15:55Z (GMT). No. of bitstreams: 1 santos_dgpo_me_bot.pdf: 1015868 bytes, checksum: 6aca3f66299016c2bab0b0b8f46c4cb4 (MD5) Previous issue date: 2016-02-29 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A espécie Mikania laevigata Sch. Bip. ex Baker, popularmente conhecida como guaco, pertence à família Asteraceae, é originária da região sul do Brasil e está entre as plantas medicinais adotadas pelo Sistema Único de Saúde do Brasil. M. laevigata é uma opção agrícola promissora no cultivo das medicinais, estando acessível ao pequeno produtor, tendo em vista a crescente demanda do mercado consumidor brasileiro por fitoterápicos. Uma vez que as plantas medicinais são classificadas como produtos naturais, a lei permite que sejam cultivadas e comercializadas desde que se atinja o padrão de qualidade necessário. O presente trabalho foi instalado e conduzido na Fazenda Experimental Lageado, da Faculdade de Ciências Agronômicas - UNESP, Campus de Botucatu, Estado de São Paulo. O objetivo desta pesquisa foi avaliar a produtividade de biomassa e teor de cumarina do guaco colhido em diferentes idades da planta. Foi observada maior produtividade para as variáveis avaliadas aos onze meses de idade do guaco, obtendo 0,96 t ha-1 de matéria seca de folha sendo que não houve diferença estatística quanto ao teor de cumarina aos 7, 9, e 11 meses de idade de Mikania laevigata. Nas condições em que foi realizada a pesquisa, o maior rendimento de biomassa x teor de cumarina foi obtido aos 11 meses de idade do guaco, o qual possibilitou o melhor resultado para o rendimento extrativo de cumarina em folhas secas. / The species Mikania laevigata Sch. Bip. ex Baker, popularly known as guaco, belongs to the Asteraceae family and it is native to southern Brazil it is among the medicinal plants adopted by the Unified Health System in Brazil (SUS). M. laevigata is a promising option in agricultural cultivation of medicinal plants and is accessible to small farmers, in view of the growing demand of the Brazilian market for herbal medicines. Since medicinal plants are classified as natural products, the law allows them to be grown and marketed it they achieve the required quality standards. This work was conducted at the Lageado Experimental Farm, Faculty of Agricultural Sciences - UNESP, Botucatu, State of São Paulo. The objective of this research was to evaluate the productivity of biomass and coumarin content of guaco harvested at different ages of the plant. It was observed higher productivity for the variables evaluated at eleven months of guaco, obtaining 0.96 t ha-1 of dry leaf and there was no statistical difference in the coumarin content at 7, 9, and 11 months of age Mikania laevigata. The conditions under which the survey was conducted, the higher biomass yield x coumarin content of guaco was obtained at 11 months of age, which enabled the best result for the extraction yield of coumarin in dry leaves. / CNPq: 133395/2014-6

This thesis investigated the pharmacology and phytochemistry of Achillea millefolium L. (yarrow) flowers, roots, stems, and leaves based on ethnobotanical reports in North America, with a focus on applications in a respiratory model. Seasonal changes in the phytochemical profile of yarrow were also assessed. A comprehensive dataset of medicinal Asteraceae was created after collecting ethnobotanical reports from the Native American Ethnobotany (NAEB) database. Using residual and binomial analyses, 14 tribes of Asteraceae were quantitatively evaluated and ranked within ten therapeutic categories as either over- or under-selected for treatment by North American indigenous peoples. Flora belonging to the Anthemideae tribe were over-utilized as pulmonary aids, particularly species of Achillea. Yarrow was selected for further analysis in the subsequent chapters of this thesis. The respiratory pharmacology of yarrow was examined by testing the immunomodulatory effects of four plant parts in an in vitro assay using BEAS-2B human bronchial epithelial cells. Concentrations of the pro-inflammatory cytokines IL-6 and IL-8 were quantified using ELISA kits. Flowers demonstrated significant anti-inflammatory activity at 40 μg/ml in both assays, and also at 20 μg/ml in the IL-8 assay, suggesting a dose-dependent response. Roots displayed significant pro-inflammatory activity at all concentrations. A second mechanism of action via the endocannabinoid system was tested through inhibitory enzyme assays for fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), in which the flowers and roots were most active. Since extracts of the four plant parts exhibited significantly different bioactivities, active metabolites previously identified in yarrow were quantified in each part through the targeted profiling of phenolics and alkylamides using analytical chromatographic techniques. Phenolic compounds were found at highest concentrations in the flowerheads, while alkylamides were detected predominantly within roots. An accompanying phenological analysis of alkylamide and phenolic levels in all parts was explored. Collectively, this research provides the first integrated comparison of yarrow ethnobotany, bioactivity, and phytochemistry across different parts of the plant, contributing novel insights into the traditional, contemporary, and future uses of one of North America’s most important medicinal plants.

PESSOA, Igor Parra. Caracterização química, atividade antioxidante e segurança de uso de sementes de Licania rigida Benth. 2015. 93 f. Dissertação (Mestrado em bioquímica)- Universidade Federal do Ceará, Fortaleza-CE, 2015. / Submitted by Elineudson Ribeiro (elineudsonr@gmail.com) on 2016-09-01T19:21:49Z No. of bitstreams: 1 2015_dis_ippessoa.pdf: 2655232 bytes, checksum: 2b3d1ecb0a344399c2327651185c3567 (MD5) / Approved for entry into archive by Jairo Viana (jairo@ufc.br) on 2016-09-02T17:53:39Z (GMT) No. of bitstreams: 1 2015_dis_ippessoa.pdf: 2655232 bytes, checksum: 2b3d1ecb0a344399c2327651185c3567 (MD5) / Made available in DSpace on 2016-09-02T17:53:39Z (GMT). No. of bitstreams: 1 2015_dis_ippessoa.pdf: 2655232 bytes, checksum: 2b3d1ecb0a344399c2327651185c3567 (MD5) Previous issue date: 2015 / Free radicals have been associated to the etiology and the progression of various chronic-degenerative diseases, and constitute one of the factors that affect food quality deterioration. There is a growing interest in finding natural and safe sources of antioxidants that are able to neutralize those damaging agents without negatively altering food sensorial characteristics. In this context, plant extracts rich in polyphenols have been investigated to this end. This study aimed to characterize the phenolic composition of the ethanolic extract (EELr) and derived fractions from Licania rigida seeds (aqueous, FALr; methanol, FMLr; ethyl acetate, FAELr; chloroform, FCLr; hexane, FHLr), to estimate the total antioxidant capacity and, at the same time, to evaluate the safe use through in vitro and in vivo toxicity tests. Phytochemical screening has detected three secondary metabolite classes from EELr: tannins, flavonoids and saponins. Moreover, it was determined the amount of total phenols, flavonoids and tannins (from 3.815 to 6.452; 0.006 to 0.135; 0.147 to 0.294 gallic acid, quercetin and tannic acid equivalents in micrograms per gram of sample, respectively). Eleven distinct phenolic compounds, classified as phenolic acids and flavonoids, were identified by HPLC. The caffeic and chlorogenic acid were the major compounds among the phenolic acids, and quercetin and kaempferol among the flavonoids. In general, the EELr, FALr, FAELr and FMLr showed antioxidant activity towards the DPPH free radical with SC50 ranging from 2.79 to 196.6 µg/mL. Regarding the inhibition of lipid peroxidation assay (using TBARS), FALr was capable of preventing lipid peroxidation both in normal conditions and in the presence of stress inducer (iron). There was a clear positive relation between the samples’ tannin content and a good performance in the antioxidant activities. Flavonoids as quercetin, quercitrin and catechin correlated positively with the results of DPPH assay and TBARS assay without iron as a stress-inducer. In the other hand, the phenolic acids, such as chlorogenic acid, showed to be more preponderant when iron was used. EELr, FALr, FAELr and FMLr showed a promising phenolic profile with potent antioxidant activity. The natural composition of L. rigida seeds can be explored in the pharmaceutical industries to produce nutraceuticals. Generally, the EELr presented low toxicity accordingly to the assays used. Nevertheless, more sensitive approaches like toxicogenomics and non-acute toxicity assays with animals must be performed to guarantee its safe use. / Radicais livres têm sido associados à etiologia e à progressão de diversas patologias crônico-degenerativas, e constituem um dos fatores de deterioração da qualidade de alimentos. Existe um crescente interesse em encontrar fontes naturais e seguras de antioxidantes capazes de neutralizar esses agentes nocivos sem alterar de forma negativa características sensoriais dos alimentos. Dentro deste contexto, extratos de plantas ricos em polifenóis têm sido investigados para esse fim. Este estudo objetivou caracterizar a composição fenólica do extrato etanólico (EELr) e frações derivadas de sementes de Licania rigida (aquosa, FALr; metanólica, FMLr; acetato de etila, FAELr; clorofórmica, FCLr; hexânica, FHLr), estimar a capacidade antioxidante total e, paralelamente, avaliar a segurança de uso através de testes de toxicidade in vitro e in vivo. Foram detectadas através de prospecção fitoquímica qualitativa três classes de metabólitos secundários no extrato: taninos, flavonoides e saponinas. Além disso, foi determinada a quantidade de fenóis totais, flavonoides e taninos do EELr e das frações FAELr, FALr e FMLr (de 3,815 a 6,452; 0,006 a 0,135; 0,147 a 0,294 equivalentes em micrograma de ácido gálico, quercetina e ácido tânico por grama de amostra, respectivamente). Onze compostos fenólicos distintos, classificados como ácidos fenólicos e flavonoides, foram identificados via CLAE. O ácido cafeico e o ácido clorogênico foram os majoritários dentre os ácidos fenólicos, e a quercetina e o kaempferol dentre os flavonoides. Em geral, o EELr, FALr, FAELr e FMLr mostraram atividade antioxidante no ensaio DPPH com CN50 variando de 2,79 a 196,6 µg/mL. Em relação ao ensaio de inibição da peroxidação lipídica (usando TBARS), a FALr foi capaz de prevenir peroxidação lipídica tanto em condições normais como na presença de indutor de estresse (ferro). Houve também uma clara relação positiva entre o conteúdo de taninos das amostras e o bom desempenho nas atividades antioxidantes. Flavonoides como a quercetina, quercitrina e catequina correlacionaram-se positivamente com o resultado do teste DPPH e do TBARS sem indução de estresse por ferro. Já os ácidos fenólicos, como ácido clorogênico, mostraram-se mais importantes quando o ferro foi usado. EELr, FALr, FAELr e FMLr mostraram perfil fenólico promissor com potente atividade antioxidante total. A composição natural das sementes dessa planta pode ser explorada na indústria farmacêutica para produzir nutracêuticos. De forma geral, o EELr apresentou baixa ou nenhuma toxicidade de acordo com os ensaios utilizados. No entanto, abordagens mais sensíveis como a toxicogenômica e ensaios de toxicidade crônica em animais devem ser feitos a fim de garantir a sua segurança de uso.

Made available in DSpace on 2014-06-11T19:34:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-23Bitstream added on 2014-06-13T20:25:35Z : No. of bitstreams: 1 rodrigues_j_dr_araiq.pdf: 2215400 bytes, checksum: 0fd02af147bd646153b8c1d9da06c642 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo desse trabalho foi a investigação da composição química de plantas do Cerrado, aplicando técnicas que permitam uma análise quali e quantitativa rápida e eficaz. As espécies estudadas neste projeto foram Miconia rubiginosa e Miconia stenostachya, pertencentes à família Melastomataceae. As espécies foram coletadas no Estado de São Paulo e os infusos foram preparados e particionados com acetato de etila e água. A fração acetato de etila da M. rubiginosa foi fracionada por Cromatografia em Contracorrente de Alta Velocidade (HSCCC), sendo isolados os compostos (-)-(2R,3R)-epicatequina (Mr1), casuarictina (Mr2), canferol-3-O-β-galactopiranosídeo (Mr3) e schizandrisídeo (Mr4). A fração acetato de etila da M. stenostachya foi fracionada por cromatografia de permeação em gel utilizando Sephadex LH-20, que possibilitou o isolamento da (+)-(2R,3S)-4’-O-metilgalocatequina (Ms1), (-)-(2R,3R)-4’-O-metilepigalocatequina (Ms2), miricetina-3-O-α-rhamnopiranosídeo (Ms3) e (-)-(2R,3R)-epicatequina (Ms4). Foram desenvolvidos métodos de separação dos enantiômeros da naringenina e catequinas por Cromatografia Líquida de Alta Eficiência acoplada a detectores de Dicroísmo Circular e Arranjo de Diodos (HPLC-CD-DAD). Os métodos desenvolvidos forneceram separação adequada com boa resolução. Foram obtidos os espectros de dicroísmo circular (CD) de todas as substâncias isoladas, permitindo a identificação dos enantiômeros. Uma metodologia de clean-up foi desenvolvida para a preparação de amostras para análise por cromatografia quiral. O método que utiliza cartucho de C18 (STRATA Phenomenex®) foi o que apresentou melhor seletividade. O método desenvolvido no HPLC-CD-DAD permitiu identificar a (-)-(2R,3R)-epicatequina no infuso de M. rubiginosa. O mesmo método foi aplicado para investigar a espécie Maytenus obtusifolia... / The objective of this project was to investigate the chemical composition of Cerrado plants, using techniques that allow a quick and efficient qualitative and quantitative analysis. In this project we studied the species Miconia rubiginosa and Miconia stenostachya which belong to the Melastomataceae family. Miconia species were collected at São Paulo State and water infusions were prepared and partitioned with EtOAc and water. The ethyl acetate fraction of M. rubiginosa was fractioned by High Speed Countercurrent Chromatography (HSCCC), and afforded (-)-(2R,3R)-epicatechin (Mr1), casuarictin (Mr2), kaempferol-3-O-β-galactopyranoside (Mr3), and schizandriside (Mr4). The ethyl acetate fraction of M. stenostachya was submitted to gel permeation chromatography over Sephadex LH-20, that led to the isolation of (+)-(2R,3S)-4'-O-methylgallocatechin (Ms1), (-)-(2R,3R)-4'-O-methylepigallocatechin (Ms2), myricetin-3-O-α-rhamnopyranoside (Ms3), and (-)-(2R,3R)-epicatechin (Ms4). Methods were developed for the enantiomeric separation of naringenin and catechins by High Performance Liquid Chromatography with Circular Dichroism and Diode Array Detectors (HPLC-CD-DAD). The developed methods provided good separation and resolution. CD spectra of all these substances were obtained, allowing the identification of the enantiomers. A clean-up methodology was developed for the preparation of plant samples previous to the chiral HPLC analysis. The method using C18-cartridge (Phenomenex STRATA®) showed the best selectivity. The method developed using HPLC-CD-DAD allowed to identify (-)-(2R,3R)-epicatechin in the infusion of M. rubiginosa. The same method was applied to investigate the commonly used... (Complete abstract click electronic access below)

Neste estudo foram obtidos os extratos etanólicos das espécies Mikania parodii Cabrera e Mikania pilosa Baker, os quais foram submetidos a fracionamento utilizando as técnicas de cromatografia líquida a vácuo, em coluna clássica e por exclusão. A partir da espécie Mikania parodii foram isolados e identificados através de comparação dos dados dos espectros de RMN 1H e 13C com a literatura os triterpenos acetato de taraxasterol e acetato de pseudotaraxasterol e os flavonóides caempferol-3-O-glicosídeo e quercetina-3-O-glicosídeo e a partir da espécie Mikania pilosa foi isolado e identificado o flavonóide quercetina 7-metil éter. Os extratos e frações de ambas as plantas foram analisados em técnicas hifenadas (CGEM, CLAE-DAD-EM/EM), permitindo a identificação de 46 substâncias em Mikania parodii e 60 substâncias em M. pilosa compreendendo as seguintes classes: monoterpenos, sesquiterpenos, um diterpeno (M. pilosa), triterpenos, flavonóides, derivados do ácido quínico (ácidos clorogênicos), ácidos graxos e seus ésteres. O extrato etanólico bruto de M. parodii apresentou atividade anticonvulsivante e antialérgica. O extrato etanólico bruto de M. pilosa ressuspendido em água : etanol (7:3) inibiu em mais de 50% e 59% respectivamente as células HCT-8 (carcinoma de cólon) e SF925 glioblastoma humano). A análise dos extratos polares de M. camporum e M. vitifolia em CLAE-DAD-EM/EM em comparação com dados da literatura permitiu a identificação dos derivados do ácido quínico: 5-O-Ecafeoilquínico, 3,5-di-O-E-cafeoilquínico, 4,5-di-O-E-cafeoilquínico e de classes de flavonóides apresentando substituintes metila e hexoses em ambas as espécies. / In this study the ethanolic extracts from the species Mikania parodii Cabrera and Mikania pilosa Baker were obtained and fractionated by vacuum liquid chromatography, column chromatography and size-exclusion chromatography. From the species M. parodii were isolated and identified through the comparison of the 1H and 13C NMR spectral data with those in the literature the triterpenes taraxasterol acetate, pseudotaraxasterol acetate and the flavonoids kaempferol-3-O-glucoside and quercetin-3-O-glucoside. From the species Mikania pilosa was isolated the flavonoid quercetin 7-methyl ether. The extracts and fractions of both plants were analyzed by hyphenated techniques (GC-MS and LC-MS/MS), allowing the identification of 46 compounds in M. parodii and 60 compounds in M. pilosa, comprised the classes: monoterpenes, sesquiterpenes, diterpene (M. pilosa), triterpenes, flavonoids, quinic acid derivatives (chlorogenic acids), fatty acids and esters. The ethanolic crude extract of M. pilosa, ressuspended in water:ethanol (7:3) inhibited more than 50 % and 59% respectively the HCT-8 (colon carcinoma) and SF925 cells (human glioblastome). The analysis of polar extracts of the M. camporum and M. vitifolia species in LC-MS/MS in comparison with literature allow the identification of quinic acid derivatives: 5-O-caffeoylquinic acid; 3,5-di-O-caffeoylquinic acid; 4,5-di-O-caffeoylquinic acid, methyl and O-glucosylflavonoids in both species.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A presente dissertação apresenta o estudo fitoquímico e avaliação biológica do extrato etanólico das folhas de Aegiphila integrifolia (Jacq.) pertencente à família Lamiaceae. O estudo fitoquímico realizado com eluato clorofómico do extrato etanólico das folhas levou ao isolamento e identificação de uma mistura de ácidos graxos na forma de seus ésteres metílicos, uma mistura de, β-sitosterol, estigmasterol e lupeol glicosilados, um flavonoide conhecido como Pectolinarigenina. As misturas de ésteres metílicos foram analisadas e determinadas por Cromatografia Gasosa. As determinações estruturais foram realizadas por meio de métodos espectrométricos mono e bidimensionais como IV, RMN de 1H (500 MHz), RMN de 13C (125 MHz), HSQC, HMBC, ESI-EM e comparação com dados da literatura. O estudo biológico do extrato etanólico apresentou um bom resultado quanto à atividade antioxidante pelo método DPPH comparado ao padrão quercetina. A investigação da toxicidade, de acordo com o teste realizado frente à Artemia salina indicou a baixa toxidade (DL 50% superior a 500 μg mL-1) e quando comparado com valores encontrados na Literatura confirma a baixa toxicidade do gênero Aegiphila frente à Artemia salina. Os ensaios da MIC para os fungos filamentosos, bactérias Gram-Positivas e Gram-Negativas e levedura, apresentaram baixa inibição comparadas com os antibióticos Ampicilina, exceto a levedura Cândida albicans. Esta apresentou inibição satisfatória, 96% aproximadamente para a amostra RR05 (do flavonoide) e 92% para amostra R06 (extrato etanólico) comparando aos antibióticos Nistatina e Miconazol (91%). / This dissertation presents the phytochemical study and biological evaluation of the ethanol extract of Aegiphila integrifolia (Jacq.) belonging to the family Lamiaceae. The phytochemical study of clorofómico eluate of ethanol leaf extract led to the isolation and identification of a mixture of fatty acids as their methyl esters, a mixture of, β - sitosterol, stigmasterol and lupeol glycosylated a flavonoid known as Pectolinarigenin. Mixtures of methyl esters were analyzed and determined by gas chromatography. Structural determinations were made by means of spectroscopic methods such as mono-and two-dimensional IR, 1H NMR (500 MHz), 13C NMR (125 MHz), HSQC, HMBC, ESI-MS and comparison with literature data. The biological study of the ethanol extract showed a good result for antioxidant activity by DPPH method compared to standard quercetin. The investigation of the toxicity of the test conducted according front Artemia salina indicated low toxicity (LD 50 % up to 500 mg mL-1) and compared to values found in literature confirming the low toxicity of the genus Artemia salina front Aegiphila. The MIC tests for filamentous fungi, Gram - Positive and Gram-Negative Bacteria and yeast showed low inhibition compared with Ampicillin antibiotics except the yeast Candida albicans. This inhibition was satisfactory, approximately 96% to RR05 sample (the flavonoid) and 92% for sample R06 (ethanol extract) comparing antibiotic Nystatin and Miconazole (91%).

Mikania é o maior gênero da tribo Eupatorieae, com cerca de 430 espécies, sendo amplamente distribuído no Brasil, com aproximadamente 200 espécies descritas. Dentro deste gênero, Mikania cordifolia, M. micrantha e M. glomerata são comumente chamadas de guaco e estão entre as espécies mais usadas popularmente, principalmente para o tratamento de febre, reumatismo, doenças do trato respiratório e contra picadas de cobra. No presente trabalho, foram realizados estudos fitoquímicos destas três espécies e foram analisados os efeitos dos tipos de adubação, da radiação solar e do estresse hídrico sobre a produção de metabólitos secundários. Primeiramente, através de estudos fitoquímicos, foram identificados 62 compostos. As frações polares das espécies apresentaram como compostos majoritários derivados fenilpropanóicos, destacando-se o Ácido 3,5-dicafeoilquínico em M. glomerata e M. micrantha e o Ácido Fertárico em M. cordifolia. Na espécie M. glomerata também foram identificados derivados do Ácido glucárico di e tri esterificados por ácidos caféicos, até o momento não descritos na literatura, além de flavonóides sulfatados, os quais também estão presentes em M. micrantha. Nas frações apolares foi verificada a presença de triterpenos, principalmente em M. cordifolia e derivados do Ácido Caurenóico em M. glomerata e M. micrantha. As lactonas sesquiterpênicas foram encontradas em M. cordifolia (esqueleto melampolido) e em M. micrantha (esqueleto micranolido). A análise dos cultivares de M. glomerata e M. cordifolia, revelou uma grande influência das condições de cultivo na composição dos metabólitos secundários. Os experimentos mostraram uma grande variação entre a concentração dos compostos presentes nas duas espécies de Mikania, sendo verificado que as condições de cultivo e principalmente as taxas de luminosidade são de extrema importância na acumulação desses metabólitos. O estresse hídrico não apontou efeitos significativos no acúmulo de substâncias em M. glomerata. As análises histoquímicas se mostraram eficazes na obtenção de informações a respeito da localização de compostos fenólicos nas folhas de M. glomerata. / Mikania is the largest gender of the tribe Eupatorieae, with about 430 species, being distributed thoroughly in Brazil, with approximately 200 described species. In this gender, Mikania cordifolia, M. micrantha and M. glomerata are commonly called \"guaco\" and are among the more popularly used species, mainly for the treatment of fever, rheumatism, diseases of the breathing tract and against snake bites. In the present work, phytochemical studies of these three species were carried out and the effects of the fertilization types, the solar radiation and the hydric stress upon the production of secondary metabolites were analyzed. Firstly, through phytochemical studies, 62 compounds were identified. The polar fractions of the species presented as majority compounds phenylpropanoic derivatives: 3,5-Dicaffeoylquinic acid in M. glomerata and M. micrantha and Fertaric acid in M. cordifolia. In M. glomerata were also identified glucaric acid derivatives di- and tri-esterified with cafeic acids, which are no described in the literature until the moment, besides sulfated flavonoids, which are also present in M. micrantha. In the apolar fractions the triterpenes presence were verified mainly in M. cordifolia and kaurenoic acid derivatives in M. glomerata and M. micrantha. The sesquiterpene lactones were found in M. cordifolia (melampolide skeleton) and in M. micrantha (micranolide skeleton). The analysis of M. glomerata and M. cordifolia cultivars revealed a great influence of the cultivation conditions in the secondary metabolites composition. The experiments showed a great variation among the concentration of the compounds in the two species of Mikania, being verified that the cultivation conditions and mainly the taxes of solar radiation are of extreme importance in the accumulation of these metabolites. The hydric stress didnt have significant effects in the accumulation of substances in M. glomerata. The histochemical analyses were effective in supply information regarding location of phenolic compounds in the leaves of M. glomerata.

Magister Scientiae - MSc / Since Helichrysum is known by the indigenous people of Africa for therapeutic properties, such as against colds, flu and wounds, the aim of this study was to focus on the patulum species found predominantly in the Western Cape region of South Africa and by means of isolation and identification of the plant constituents, be able to relate the therapeutic activity on the basis of literature precedents, to the compounds extracted. / South Africa

For over a century, documented scientific research and debate has revolved around the therapeutic properties of the medicinal plant Echinacea angustifolia. With overwhelming evidence demonstrating the biological activity of its root phytochemical constituents, the genetic improvement of E. angustifolia by selecting phytochemically rich genotypes has garnered both scientific and commercial interest. This dissertation presents results of multi-disciplinary experiments intended to help establish scientifically based guidelines for breeding efforts aimed at developing therapeutically superior varieties of E. angustifolia in British Columbia. Cultivated E. angustifolia populations from British Columbia and Washington were grown in a common greenhouse environment to identify possible genetically superior populations with respect to root concentrations of therapeutically relevant caffeic acid derivatives (CAD) and alkamides. However, none of the studied cultivated E. angustifolia populations showed significant genetic differences in terms of root phytochemical traits. In the second part, an investigation into correlations between root and shoot phytochemical concentrations in field- and greenhouse-grown plants revealed that concentrations of therapeutically relevant marker compounds in shoots were generally poor predictors of concentrations in roots. Some weak yet significant positive correlations were observed between root and shoot concentrations of CADs but were inconsistent between the two environments. Significant genotype by environment interactions were documented for the first time in phytochemical traits of E. angustifolia in a study of five genetically homogeneous populations grown in three different environments, including 1 greenhouse and 2 field sites in British Columbia. For the final objective, in vitro bioassays showed that environmentally and genotypically related differences in concentrations of CADs and alkamides in E. angustifolia ethanolic root extracts did not translate into significant differences in their anti-inflammatory potential as measured by pro-inflammatory interleukin (IL-6 and IL-8) secretion in human bronchial epithelial (BEAS-2B) cells challenged with rhinovirus. When used in isolation however, pure tetraene alkamide showed a significant inhibitory effect on secretion, thereby further supporting the use of high alkamide production as a selection criterion for therapeutic E. angustifolia cultivar development. A series of recommendations derived from these findings are presented along with ideas for important future studies in the field of Echinacea research. / Land and Food Systems, Faculty of / Graduate