Improving diversity of food systems by targeting whole grain cereals, pseudo-cereals, and millets is essential to enhance nutritional qualities beyond macro and micronutrient balance and to address emerging global food and nutritional security-linked public health challenges. However, human health relevant nutritional parameters of whole grains vary widely among species, genotypes, growing conditions, and further due to different processing methods. Therefore, it is important to screen human health relevant nutritional parameters of these whole grains prior to targeting them for wider public health solutions linked to non-communicable chronic diseases (NCD). Based on this rationale, oats from different processing stages and from different production systems, buckwheat, teff, pearl millet, and different genotypes of sorghum were analyzed for health relevant phenolic bioactive linked antioxidant and anti-hyperglycemic properties using in vitro assay models. Overall, high phenolic-linked antioxidant and anti-diabetic properties were observed in whole grain oats, rolled oat, buckwheat, teff, and select sorghum genotypes.

Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná / Extratos, óleos essenciais e compostos químicos isolados de origem vegetal têm sido cada vez mais utilizados, não só como matéria-prima para indústrias de diversos ramos, mas também como alternativa no tratamento de problemas da saúde pela população em geral. Considerando a expressiva importância de produção destas substâncias com qualidade elevada e preço acessível, o presente trabalho teve como objetivo a análise técnica e econômica na obtenção de compostos bioativos a partir das espécies vegetais Artemisia annua e Varronia curassavica. Visando selecionar e testar três tecnologias de extração ambientalmente sustentáveis, dióxido de carbono supercrítico, maceração a frio com o solvente etanol e destilação com arraste a vapor, um protocolo de alto rendimento e baixo custo para obtenção de compostos bioativos de plantas foi proposto. Para a extração com dióxido de carbono supercrítico foi realizada a investigação da influência da temperatura, pressão e volume de cossolvente (etanol) no rendimento de extração e pureza dos extratos. Três experimentos com delineamento inteiramente casualizado em arranjo fatorial foram realizados. Para o experimento com A. annua foram testadas 3 temperaturas (40/50/60 ºC), 3 pressões (200/250/300 bar) e 3 níveis de cossolvente (0/15/25%); e para V. curassavica 2 temperaturas (40/60 ºC), 5 pressões (100/150/200/250/300 bar) e extração fracionada. As extrações com destilação por arraste a vapor foram conduzidas à pressão ambiente por 3 - 4 h. E a maceração a frio com etanol foi realizada em série, a pressão ambiente por 6 h, condições estas as ótimas referenciadas. Ao fim dos experimentos os rendimentos e pureza dos extratos e óleo essencial foram comparados e utilizados para a implementação de indústrias de produção de biocompostos utilizando as tecnologias testadas. Por meio de pesquisa de custos envolvidos na implementação do projeto, uso de planilhas no Microsoft Office Excel, do Software SuperPro Designer® e do Aplicativo Web $AVEPI, foi possível estimar os Custos de Produção e Manutenção, Capital Fixo Direto, e, na sequencia simular computacionalmente os cenários econômicos, gerando os indicadores de viabilidade e riscos de implantação das indústrias de extração de artemisinina à partir de A. annua, e óleo essencial à partir de V. curassavica. Observou-se que a extração de artemisinina com dióxido de carbono supercrítico obteve menores rendimentos de extrato que a extração com etanol, porém com maior pureza do composto alvo e custos menores de produção. Na produção de óleo essencial de V. curassavica a extração com dióxido de carbono supercrítico alcançou os mesmos rendimentos e pureza obtidos por destilação com arraste a vapor. No cenário estudado os custos de operação e manutenção da produção de extratos com etanol, dióxido de carbono supercrítico, para A. annua, e dióxido de carbono supercrítico para V. curassavica, revelaram ser maiores que o preço de revenda dos extratos. Para a planta A. annua tais resultados foram atribuídos aos altos custos da matéria-prima, e para V. curassavica aos baixos rendimentos de extrato. O projeto de investimento utilizando destilação com arraste a vapor para obtenção de óleo essencial de V. curassavica mostrou ser promissor devido à alta rentabilidade e baixo risco associado nos senários previstos. / Extracts, essential oils and isolated chemical compounds of vegetable origin have been increasingly used, not only as raw material for industries of different branches, but also as an alternative in the treatment of health problems by the population in general. Considering the expressive importance of producing these substances with high quality and affordable price, the present work had the objective of the technical and economic analysis in obtaining bioactive compounds from the plant species Artemisia annua and Varronia curassavica. Aiming to select and test three environmentally sustainable extraction technologies, supercritical carbon dioxide, cold maceration with the ethanol and steam distillation, a protocol of high yield and low cost to obtain bioactive compounds of plants was proposed. For the supercritical carbon dioxide extraction, the influence of temperature, pressure and volume of cosolvent (ethanol) on the extraction yield and purity of the extracts was investigated. Three experiments with a completely randomized design in factorial arrangement were performed. For the A. annua, three temperatures (40/50/60 ºC), 3 pressures (200/250/300 bar) and 3 levels of cosolvents (0/15/25%) were tested; and for V. curassavica 2 temperatures (40/60 ºC), 5 pressures (100/150/200/250/300 bar) and fractional extraction. The extractions with steam distillation were conducted at ambient pressure for 3 - 4 h, and cold maceration with ethanol was carried out in series, at ambient pressure for 6 h, conditions being the best referenced. At the end of the experiments the yields and purity of the extracts and essential oil were compared and used for the implementation of industries of biocomposites production using the technologies tested. Through the research of costs involved in the project implementation and the use of spreadsheets in Microsoft Office Excel, it was calculated the Costs of Production and Maintenance and Direct Fixed Capital; on the sequence, using the Software SuperPro Designer® and the Web Application $AVEPI, the computational simulations were conducted generating the economic indicators on the feasibility and risks of implantation of the industries of extraction of artemisinin from A. annua, and essential oil from V. curassavica. It was observed that the extraction of artemisinin with supercritical carbon dioxide obtained lower yields of extract than the extraction with ethanol, but with higher purity of the target compound and lower costs of production. In the production of essential oil of V. curassavica the extraction with supercritical carbon dioxide reached the same yields and purity obtained by steam distillation. In the scenario studied the costs of operation and maintenance of the production of extracts with ethanol, supercritical carbon dioxide for A. annua, and supercritical carbon dioxide for V. curassavica, were shown to be greater than the revenue price of the extracts. For the A. annua plant, these results were attributed to the high costs of the raw material, and to V. curassavica the low yields of the extract. The investment project using steam distillation for the obtaining of V. curassavica essential oil showed to be promising due to the high profitability and low risk associated in the expected scenarios.

Orientador: Anderson Marliere Navarro / Banca: Camila de Moraes / Banca: Thabata Koester Weber / Resumo: O diabetes mellitus tipo 1 (DM1) é uma doença autoimune caracterizada pela diminuição da produção de insulina pelo pâncreas sendo o principal mecanismo fisiopatológico a infiltração de células inflamatórias, liberação de citocinas pró-inflamatórias e consequente destruição das células beta pancreáticas. Objetivo: testar o possível efeito anti-inflamatório da suplementação de curcumina e do exercício físico aeróbio de moderada intensidade sobre o desenvolvimento do DM1 em camundongos non-obese diabetic (NOD). Métodos: foram selecionados 48 camundongos NOD com cinco semanas de vida e divididos em quatro grupos (n=12): controle (C), suplemetados com curcumina (CUR), treinados (T) e por último o grupo treinado e suplementado (TC). O experimento durou 20 semanas, a cada duas semanas era medida a glicemia através de glicosimetro. Animais que apresentaram glicemia >250 mg/dL foram classificados como diabéticos. No final foi analisado distribuição de insulites no pâncreas, citocinas inflamatórias, insulina e glicemia de jejum no soro. Resultados: Após 25 semanas de vida a incidência de diabetes foi baixa em todos os grupos (0-16,6%) e não houve diferença entre os grupos nos valores finais de glicemia de jejum. Entretanto, foi possível observar que os animais dos grupos que treinaram apresentaram menos insulites comparados com os grupos sedentários. Não houve efeito da suplementação de curcumina. Conclusão: o exercício físico, mas não a suplementação de curcumina, previne insulites de... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Type 1 diabetes (T1D) is an autoimmune disease characterized by decreasing of pancreas insulin production. The main pathophysiological mechanism is immune cell infiltration, release of inflammatory cytokines and consequent destruction of beta pancreatic cells. Objective: it is to test possible anti-inflammatory effects of curcumin supplementation and moderate-aerobic exercise on development of T1D in non-obese diabetic mouse (NOD). Methods: At five weeks old, forty-eight NOD were randomly separated into four groups (n=12): control (C), curcumin (CUR), trained (T), and trained plus curcumin (TC). Experiment lasted 20 weeks; every two week glycemic was measured by glucometer. Animals which had glycemic more than 250 mg/dL were classified as diabetic. In the final of protocol, insulits, cytokines and insulin were measured. Results: After 20 weeks, all groups showed low diabetes incidence (0-16.6%), and there were no difference in fasting blood glucose between groups. However, the two groups of trained animals had less insulitis than other sedentary groups. Curcumin supplementation had any effects. Conclusion: exercise, but not curcumin supplementation, prevents insulitis in NOD mice... (Complete abstract click electronic access below) / Mestre

Commercial marrubiin, aqueous and organic extracts of Leonotis leonurus were tested in vitro for their anticoagulant and antiplatelet activities. The aqueous extract inhibited platelet aggregation by 69.5 percent (100 μg/mL), while the organic extract (100 μg/mL) and marrubiin (5 μg/mL) showed 92.5 percent and 91.6 percent inhibition, respectively, by inhibiting the binding of fibrinogen to glycoprotein IIb/IIIa receptor in a concentration dependent manner. The extracts significantly prolonged activated partial thromboplastin time compared to untreated plasma controls. Fibrin and D-Dimer formation were drastically decreased. The extracts and marrubiin concentration-dependently inhibited calcium mobilization induced by collagen and thrombin. The formation of thromboxane A2 was also significantly reduced by both the extracts and marrubiin. Protein secretion and platelet adhesion were significantly reduced by both the extracts and marrubiin. The organic extract and marrubiin showed a more pronounced effect than the aqueous extracts in all the in vitro assays. The ex-vivo animal model confirmed the results obtained in vitro. Similar to the in vitro studies, activated partial thromboplastin time clotting time was prolonged by marrubiin and the number of aggregated platelets were significantly reduced relative to aspirin. The findings reflect that marrubiin largely contributes to the organic extract's anticoagulant and antiplatelet effect in vitro. INS-1 cells were cultured under normo- and hyperglycaemic conditions. Marrubiin and the two Leonotis leonurus extracts were screened for anti-diabetic activity in vitro. The stimulatory index of INS-1 cells cultured under hyperglycaemic conditions was significantly increased by 60 percent and 61 percent (p<0.01; n=5) in cells exposed to the organic extract (10 μg/mL) and marrubiin (500 ng/mL), respectively, relative to the normoglycaemic conditions. The gene expression of insulin was significantly increased by 76.5 and 71 percent, and of glucose transporter-2 by 93 and 92.5 percent for marrubiin and the organic extract, respectively, under the same conditions stipulated above (p<0.01; n=4). The extract and marrubiin similarly showed an increase in respiratory rate under hyperglycaemic conditions. Marrubiin increased insulin secretion, HDL-cholesterol, while it decreased total cholesterol, LDL-cholesterol and the atherogenic index in the in vivo rat model.

[Truncated abstract] Antimicrobial growth promoters are added to feed to prevent lactic acidosis in ruminant animals by selectively inhibiting rumen bacteria that produce lactic acid. However, recently imposed or impending bans on the use of antimicrobial growth promoters in animal production have lead to a critical need to find practical alternatives that are safe for the animal and consumer and that obtain similar production benefits. I investigated bioactive plants of Australia for their potential to prevent lactic acidosis in ruminants. The unifying hypothesis tested was that plants would be identified that selectively inhibit lactic acid-producing bacteria and consequently protect against lactic acidosis. This hypothesis was tested in a three phase process: phase 1, plant selection and collection; phase 2, a three stage protocol for screening plants and essential oils; phase 3, in vivo experiments and chemical fractionation of the most promising plant. I developed an in vitro bioassay that simulated acidosis by adding glucose to rumen fluid in Bellco tubes and incubating for 5 h (Chapter 4). The pH and gas production were used as indicators of acidosis and fermentation activity. I used this bioassay to screen ninety-five plants (dried and ground material from 79 species) and ten essential oils and included a negative control (oaten chaff) and a positive control (virginiamycin). One plant, Eremophila glabra, produced a similar pH (5.63) to the positive control (5.43) although it inhibited gas production to a moderate extent (P < 0.05). ... Seven serrulatane diterpenes were identified to be the major secondary metabolites in E. glabra. The metabolites were screened using a broth dilution and microtitre spectrophotometry method and were selective against S. bovis at between 320 and 1077 [mu]g/ mL. The serrulatanes from E. glabra were probably responsible for the activity against acidosis that I observed in vitro, because they selectively inhibited lactateproducing bacteria. It is also possible that a synergy between serrulatanes and possibly other metabolites are responsible for the activity observed in vitro. The results from my experiments support the role that bioactive plants may have to replace the antibiotics that are added to livestock feed. Australian plants were identified containing compounds that were active against the bacterial processes responsible for ruminant acidosis. To my knowledge this is the first work undertaken to identify bioactive plants of Australia for their potential to prevent acidosis. I developed in vitro screening bioassays that targeted key indicators of acidosis. These bioassays enabled me to identify 5 plants from the 104 screened that could potentially control acidosis. One of these plants in particular, E. glabra, showed a level of activity in vitro that was comparable to antibiotic protection against acidosis. The exciting in vitro results were not demonstrated in vivo but only one dose level of E. glabra was used, which was based on the in vitro work. In contrast to the in vitro system the rumen is a continuous flow system with greater complexity and it is possible that the concentration of E. glabra that I used in vivo was not optimum. This places importance on future dose response experiments to confirm the efficacy of E. glabra in vivo.