Orientador: Neura Bragagnolo / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-10-03T13:46:21Z (GMT). No. of bitstreams: 1 Alves_AdrianaBarreto_D.pdf: 4493430 bytes, checksum: b528cf0688daea5421cc2af99d689e45 (MD5) Previous issue date: 2009 / Resumo: Estudos epidemiológicos têm demonstrado que o consumo de frutas e vegetais tem um efeito benéfico na redução da incidência de várias doenças como o câncer e doenças cardiovasculares. Esse efeito tem sido relacionado com a presença de compostos antioxidantes nesses alimentos, sobretudo os flavonóides. O tomate (Lycopersicum esculentum Mill.) é um dos vegetais mais consumidos no mundo, in natura ou processado, e também é rico em compostos antioxidantes como carotenóides, vitaminas e flavonóides. Os alimentos processados, frequentemente, são tidos como menos nutritivos que os alimentos in natura, devido, principalmente, ao fato de que alguns nutrientes são degradados pelas altas temperaturas empregadas. Assim, torna-se importante avaliar o efeito do processamento e da estocagem sobre os compostos antioxidantes do tomate e também sobre sua atividade antioxidante. Um planejamento experimental foi realizado para otimizar as condições de extração dos compostos fenólicos e concentração dos flavonóides em polpa de tomate concentrada. O método otimizado foi validado para as determinações de compostos fenólicos totais e flavonóides totais por espectrofotometria e também para a determinação de flavonóides por cromatografia líquida de alta eficiência (CLAE). Os métodos espectrofotométricos foram validados nos parâmetros repetibilidade e exatidão. A determinação de flavonóides por CLAE foi validada nos parâmetros seletividade, linearidade, precisão, exatidão e sensibilidade. O efeito do processamento e da estocagem sobre os compostos antioxidantes do tomate foi avaliado. Foram analisados os teores de compostos fenólicos totais, flavonóides totais, flavonóides por CLAE, ácido ascórbico, licopeno e ß-caroteno, bem como a atividade antioxidante das frações hidrofílicas e lipofílicas pelos métodos ABTS e DPPH. Verificou-se que, durante o processamento, em geral, não houve perdas dos compostos antioxidantes. Durante o armazenamento, observou-se grande degradação do ácido ascórbico, porém, os demais compostos mantiveram-se estáveis, e não foi observada nenhuma alteração na atividade antioxidante. O efeito do processamento sobre a atividade antioxidante do extrato fenólico foi também avaliado por espectroscopia de ressonância de elétron-spin (ESR) usando sal de Fremy e em sistema-modelo de lipossomas. Esses e os outros resultados de atividade antioxidante obtidos previamente foram correlacionados com os teores de compostos fenólicos totais a fim de melhor estudar os mecanismos de ação antioxidante envolvidos. A ação antioxidante das amostras de tomate, coletadas em diferentes etapas do processamento, foi testada em carne de frango processada sob alta pressão a 300, 600 e 800 MPa e armazenada sob refrigeração por 15 dias. A adição de 0,30% de subproduto (pele + semente) ou 0,10% de polpa concentrada resultou em uma fase lag de 6 dias para a formação de produtos secundários da oxidação lipídica na carne de frango processada a 600 MPa. O subproduto apresentou efeito similar também para a carne de frango processada a 800 MPa. O resultado deste trabalho mostrou que, embora o processamento e a estocagem de polpa de tomate possam ter degradado substâncias mais sensíveis como o ácido ascórbico, os demais compostos antioxidantes não sofreram alterações deletérias, e, para alguns, o processamento foi benéfico, aumentando sua disponibilidade. De forma semelhante, as atividades antioxidantes dos produtos processados foram iguais ou maiores que as das amostras in natura e se mantiveram estáveis durante o armazenamento por um ano. Além disso, o subproduto do processamento pode ter boas chances de aplicação como antioxidante em outros produtos alimentícios / Abstract: Epidemiological studies have shown that the consumption of fruits and vegetables has a beneficial effect on reducing some diseases like cancer and cardiovascular diseases. These benefits have been associated to the presence of antioxidant compounds in those foods, mainly flavonoids. Tomato (Lycopersicum esculentum Mill.) is one of the most worldwide consumed vegetables, in natura or processed. Moreover, tomato is rich in many antioxidant compounds like carotenoids, vitamins and flavonoids. Frequently, thermoprocessed foods are taken as less healthy than in natura foods, mainly because nutrient losses caused by high temperature. So, it is very important to evaluate the effect of processing and storage on tomato antioxidant compounds and on their antioxidant activity. A response surface methodology was used to optimize the phenolics extraction conditions and flavonoids concentration from concentrated tomato paste. The optimized method was validated for total phenolics and total flavonoids spectrophotometric determinations and also for flavonoids quantification by high performance liquid chromatography (HPLC). The spectrophotometric methods were validated for repeatability and recovery. Flavonoids determination by HPLC was validated for selectivity, linearity, precision, recovery and sensibility. Processing and storage effect on tomato antioxidant compounds was evaluated. Total phenolics, total flavonoids, flavonoids by HPLC, ascorbic acid, lycopene and ß-carotene were determined and also the antioxidant activity of hydrophilic and lipophilic fractions were studied using ABTS and DPPH methodologies. It was observed that during processing, in general, there was no loss of the antioxidant compounds present in tomato. During the storage time there was a great loss of ascorbic acid, but all other antioxidant compounds were stable and no changes in their antioxidant activity were observed. The effect of tomato paste processing on the antioxidant activity of phenolic extract was also analyzed through electron-spin resonance spectroscopy (ESR) using Fremy¿s salt, and in a liposome model-system. These and the other antioxidant activity results previously obtained were correlated with the total phenolics content found in the samples in order to better study the antioxidant mechanisms involved. The antioxidant action of tomato samples, collected at different processing steps, was analyzed during 15 days chill storage of high-pressure treated chicken meat balls at 300, 600, and 800 MPa. Addition of 0.30% tomato waste (skin + seeds) or of 0.10% final tomato paste to minced meat led to a lag phase of 6 days for formation of secondary oxidation products in meat treated at 600 MPa. The waste product seemed especially efficient in protecting chicken meat pressurized at 800 MPa, as a notably lower rate of formation of secondary oxidation products was found. This work showed that, although processing and storage of tomato paste might result in loss of the most labile substances like ascorbic acid, the other antioxidant compounds were not affected, and, for some of them, processing increased their availability. Similarly, the antioxidant activities of final products were equal to or greater than the in natura ones and remained unaltered during one year storage. In addition, waste material may have good chances of application as antioxidant in other foods / Doutorado / Ciência de Alimentos / Doutora em Ciência de Alimentos

Orientador: Eliana Aparecida Varanda / Banca: Eliana Aparecida Varanda / Banca: Marcelo Aparecido da Silva / Banca: Luís Vitor Silva do Sacramento / Resumo: A família Eriocaulaceae possui cerca de 1200 espécies divididas em 10 gêneros e suas espécies de plantas são conhecidas como sempre-vivas, por sua grande durabilidade e coloração paleácea. Neste trabalho foram estudadas as espécies: Eriocaulon ligulatum, Leiothrix flavescens e Leiothrix spiralis, as quais foram avaliadas quanto à mutagenicidade e estrogenicidade e algumas substâncias isoladas foram utilizadas para um estudo de relação estrutura-atividade mutagênica e estrogênica. Para avaliação da mutagenicidade, utilizou-se o teste de Ames, e o teste RYA (Recombinant Yeast Assay) foi o empregado para avaliação da estrogenicidade. Os resultados da atividade mutagênica demonstraram que apenas E. ligulatum foi considerado mutagênico e isso foi atribuído às isocumarinas e flavonóides agliconas. Os estudos de relação estrutura-atividade mutagênica mostraram que esta ação foi devida à presença de hidroxilas em posições estratégicas e à ausência de glicosilações, metoxilações, ou qualquer outro tipo de substituição. Para complementar os estudos de relação estrutura-atividade mutagênica com as isocumarinas, utilizou-se resultados já publicados de mutagenicidade de moléculas semelhantes à isocumarina eriocaulina, isolada de E. ligulatum. Verificou-se que os dímeros de isocumarinas têm a sua mutagenicidade influenciada pela conformação espacial, pela presença de grupos hidroxilas mais afastados de grupos volumosos, e pelo tipo de ligação que une os seus monômeros. Quando o potencial estrogênico foi avaliado, apenas a L. flavescens apresentou resultados positivos e que esses são devidos à presença de flavonas agliconas, como a luteolina e a metoxiluteolina. As mesmas isocumarinas, pertencentes a outras espécies da família Eriocaulaceae, avaliadas no teste de Ames, foram avaliadas no teste RYA... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Eriocaulaceae family comprises around 1200 species, divided into 10 genera, and their plant species are known as "sempre-vivas" (everlasting flowers) for its durability and color. In this work the species Eriocaulon ligulatum, Leiothrix flavescens and Leiothrix spiralis were studied. These species were evaluated for the mutagenic and the estrogenic potential and some of their isolated compounds were used for a study of structuremutagenic and estrogenic activities. To assess mutagenicity we used Ames test and the Recombinant Yeast Assay (RYA test) was used for evaluation of estrogenicity. The results of mutagenic activity showed that only E. ligulatum presented mutagenicity and that these results were due to its naphthopyranones and flavonoid aglicons. The structuremutagenic activity studies shown that this action were due to the presence of hydroxyl groups in strategic positions and no glycosylations, methoxylation or any type of substitutions. To complement the studies of structure-mutagenic activity with the naphthopyranones, we use results already published of the mutagenicity of similar compounds to the naphthopyranone eriocaulina, isolated from E. ligulatum, and compare them with the data from ericauline. It was found that the dimers of naphthopyranones have their mutagenicity influenced by its spatial conformation, for the presence of hydroxyl groups furthest away from large groups, and the type of connection that join their monomers. When the estrogenic potential was assessed, we found that only L. flavescens showed positive results and that these results are due to the presence of flavones in the form of aglycones, such as luteolin and methoxyluteolin. The same naphthopyranones belonging to other species of Eriocaulaceae family, evaluated in the Ames test, were assessed in the RYA test. Their results were crucial for the establishment of structureestrogenic activity... (Complete abstract click electronic access below) / Mestre

乳腺癌是女性最常見的腫瘤之一，多發生在女性絶經後，並具有雌激素依賴性。芳香化酶(CYP19)是雌激素生物合成過程中的關鍵酶，而芳香化酶抑製劑(AI)則被用於替代治療雌激素依賴性的乳腺癌。然而，AI在降低雌激素水平的同時能夠引起骨質酥鬆。此項研究的目的是找尋AI替代物。 / 黃酮類化合物是一種多酚化合物，廣泛分佈于植物中。我們先前的研究發現二氢黄酮陈皮素能夠抑制芳香化酶的生物活性，并且抑制芳香化酶高表達的乳腺癌生長。在本研究中，我們發現陳皮素在抑制腫瘤生長的同時能夠降低来曲唑引起的骨質流失。木犀草素是另外一種黄酮类化合物，它同樣能夠抑制芳香化酶的活性并減少骨流失。而與陳皮素不同的是，它能夠抑制芳香化酶的表達。在芳香化酶高表達的乳腺癌細胞(MCF-7 aro)中，木犀草素抑制芳香化酶活性的IC50是3 μM。在MCF-7 細胞中，5 μM的木犀草素能夠抑制CYP19 mRNA 的表達，螢光素酶報告實驗顯示木犀草素是通過作用于啟動子I.3和II來抑制CYP19的表達。蛋白印跡實驗表明木犀草素抑制CYP19表達的分子機制可能通過調節JNK信號通路進而減少AP-1的活性來實現。動物實驗結果顯示木犀草素能夠抑制MCF-7aro腫瘤的生長并改善來曲唑引起的骨流失。 / 環氧化酶(COX)是花生四烯酸轉化為前列腺素途徑中的一種關鍵酶。研究發現COX-2在乳腺癌組織中廣泛表達。本實驗研究了COX抑製劑在裸鼠動物模型中對乳腺癌腫瘤的作用機制。研究結果表明塞來昔布和阿司匹林在不影響血液中雌激素水平的情況下抑制乳腺癌腫瘤的生長。蛋白印迹實驗顯示這兩種藥物能夠降低腫瘤中COX-2，Cyclin A和Bcl-xL的表達。miR-98, miR-222和miR-145也能夠被塞來昔布和阿司匹林影響。 / 本研究表明陳皮素，木犀草素及COX抑制劑有潛力成為替代AI的化學治療藥物或共同治療藥物。 / Breast cancer is one of the most prevalent cancers affecting women. The majority of breast tumor growth occurred in the post-menopausal period are estrogen dependent. Aromatase (CYP19) catalyzes the rate-limiting step in the synthetic reaction of estrogen and aromatase inhibitors (AIs) are contemporary treatment for estrogen-positive breast cancer. However, estrogen-lowering drugs may promote osteoporosis. Our objective of this study further identified some alternatives for AIs. / Flavonoids are polyphenolic compounds that are ubiquitously distributed in plants. We have previously found that the flavanone hesperetin can inhibit the activity of aromatase and suppress aromatase-expressing breast tumor growth. In this project, we investigated the potential interaction between hesperetin and the AI letrozole in a mouse model. Our results showed that hesperetin could inhibit the tumor growth and reduce bone loss induced by letrozole. Similarly, another flavonoid luteolin also inhibited aromatase and prevented bone deterioration as observed in this project. In cells stably transfected with CYP19 (MCF-7aro), luteolin inhibited the aromatase activity with an IC50 value of 3μM. In addition, 5μM luteolin significantly reduced CYP19 mRNA expression in MCF-7 cells. Luciferase reporter assay revealed that luteolin could suppress CYP19 transcription at promoter regions I.3 and II. Western analysis illustrated that JNK signaling pathway was involved and deactivation of AP-1 could be the underlying molecular mechanism. Subsequently, we examined the effect in vivo. Our results showed that luteolin could inhibit the MCF-7aro tumor growth and improved bone loss induced by letrozole. / Cyclooxygenase (COX) is an enzyme responsible for the conversion of arachidonic acid into prostaglandins. It is over-expressed in breast cancer tissue and an increased expression of COX-2 was also observed in the xenograft model employed in this project. In the last study we evaluated the importance of COX-2 in breast tumor growth in this model. Our data showed that celecoxib and aspirin could significantly suppress the tumor growth without changing the plasma estrogen level. Western analysis illustrated that COX-2, Cyclin A, Bcl-xL and ER were reduced in celecoxib- and aspirin- treated tumor samples and miR-98, miR-222 and miR-145 were altered by celecoxib or aspirin. / After all, this project demonstrated that hesperetin, luteolin and COX-inhibitors could be potential chemopreventive or co-therapeutic agents. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Fengjuan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 131-148). / Abstract also in Chinese. / ACKNOWLEDGEMENTS --- p.I / ABSTRACT --- p.II / 摘要 --- p.IV / LIST OF ABBREVIATIONS --- p.V / TABLE OF CONTENTS --- p.VII / CHAPTER 1 --- p.1 / GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- Types of Breast Cancer --- p.3 / Chapter 1.2 --- Nuclear Receptor Signaling Pathways in Breast Cancer --- p.5 / Chapter 1.3 --- Estrogen and Breast Cancer --- p.7 / Chapter 1.4 --- Estrogen and Bone Health --- p.8 / Chapter 1.5 --- Estrogen Biosynthesis and Aromatase --- p.10 / Chapter 1.6 --- Tissue Specific Promoter for Aromatase Expression --- p.13 / Chapter 1.7 --- Nuclear Receptors and Aromatase Promoter Regulation --- p.15 / Chapter 1.8 --- Signaling Pathway and Aromatase Expression --- p.17 / Chapter 1.9 --- Cell Cycle in Breast Cancer --- p.20 / Chapter 1.10 --- Cell Apoptosis --- p.23 / Chapter 1.11 --- Treatment of breast cancer --- p.25 / Chapter 1.12 --- Phytoestrogens --- p.29 / Chapter 1.13 --- Aim of My Study --- p.32 / CHAPTER 2 --- p.33 / MATERIALS AND METHODS --- p.33 / Chapter 2.1 --- Chemicals and Materials --- p.33 / Chapter 2.1.1 --- Chemicals --- p.33 / Chapter 2.1.2 --- Plasmids --- p.33 / Chapter 2.2 --- Cell Culture --- p.33 / Chapter 2.3 --- Aromatase Activity Assay --- p.34 / Chapter 2.4 --- Quantitative Real Time PCR --- p.36 / Chapter 2.4.1 --- RNA Isolation and cDNA Synthesis --- p.36 / Chapter 2.4.2 --- Quantitative Real Time PCR Assay --- p.37 / Chapter 2.4.3 --- MiRNA Quantitative Real Time PCR Assay --- p.38 / Chapter 2.5 --- Western Blot --- p.39 / Chapter 2.6 --- Measurement of Promoter Activity --- p.41 / Chapter 2.6.1 --- Plasmid Preparation --- p.41 / Chapter 2.6.2 --- Transient Transfection and Dual-Luciferase Assay --- p.42 / Chapter 2.7 --- Electrophoretic Mobility Shift Assay (EMSA) --- p.43 / Chapter 2.7.1 --- Nuclear protein extraction --- p.43 / Chapter 2.7.2 --- Electrophorectic Mobility Shift Assay --- p.44 / Chapter 2.8 --- Animal Experiment Design --- p.45 / Chapter 2.8.1 --- Animal Model for Hesperetin Study --- p.45 / Chapter 2.8.2 --- Animal Model for Luteolin Study --- p.46 / Chapter 2.8.3 --- Animal Model for Cycooxygenase Inhibitors Study --- p.48 / Chapter 2.8.4 --- Serum Estradiol Determination --- p.49 / Chapter 2.8.5 --- Analysis of serum lipoproteins --- p.49 / Chapter 2.8.6 --- Bone Image Acquisition and Region of Interest Selection --- p.50 / Chapter 2.9 --- Statistical Analysis --- p.50 / CHAPTER 3 --- p.51 / The citrus flavonone hesperetin prevents letrozole- induced bone loss in a mouse model of breast cancer --- p.51 / Chapter 3.1 --- Introduction --- p.51 / Chapter 3.2 --- Results --- p.54 / Chapter 3.2.1 --- Murine Body Weight and Liver Weight --- p.54 / Chapter 3.2.2 --- Effect of Hesperetin and Letrozole on Xenograft Growth in Ovariectomized Mice --- p.55 / Chapter 3.2.3 --- Hesperetin Reduced Plasma Estradiol Concentration --- p.58 / Chapter 3.2.4 --- PS2 mRNA Expression in Tumor --- p.59 / Chapter 3.2.5 --- Uterine Wet Weight --- p.60 / Chapter 3.2.6 --- Hesperetin Prevent Bone Deterioration Induced by Letrozole --- p.61 / Chapter 3.3 --- DISCUSSION --- p.63 / CHAPTER 4 --- p.66 / dIETARY FLAVONOID LUTEOLIN ON cyp19 transcription in the breast cancer cells mcf-7 --- p.66 / Chapter 4.1 --- Introduction --- p.66 / Chapter 4.2 --- Results --- p.68 / Chapter 4.2.1 --- Inhibitory Effect of Luteolin on Aromatase Activity --- p.68 / Chapter 4.2.2 --- Luteolin Reduced Aromatase mRNA Expression in MCF-7 Cells --- p.70 / Chapter 4.2.3 --- Effect of Luteolin on Promoter I.3/II Activity of CYP19 in MCF-7 Cells --- p.71 / Chapter 4.2.4 --- The Effect of Luteolin on Truncation CYP19 Gene Reporter Assay --- p.72 / Chapter 4.2.5 --- Luteolin Reduced AP-1 Binding in Promoter I.3/II DNA Fragment --- p.74 / Chapter 4.2.6 --- Inhibitory Effect of Luteolin on Protein Kinase Signaling --- p.76 / Chapter 4.3 --- Discussion --- p.78 / CHAPTER 5 --- p.83 / interaction OF LUTEOLIN and letrozole in a postmenopausal breast cancer model --- p.83 / Chapter 5.1 --- Introduction --- p.83 / Chapter 5.2 --- Results --- p.86 / Chapter 5.2.1 --- Luteolin and letrozole treatment had no effect on mouse body weight and liver weight --- p.86 / Chapter 5.2.2 --- Effect of luteolin and Letrozole on Xenograft Growth in Ovariectomized Mice --- p.88 / Chapter 5.2.3 --- Luteolin reduced plasma estradiol concentration --- p.91 / Chapter 5.2.4 --- Luteolin Counteracted Uterine Weight Reduction under Letrozole Treatment --- p.92 / Chapter 5.2.5 --- Luteolin Prevented Bone Deterioration Induced by Letrozole --- p.93 / Chapter 5.2.6 --- The Effect of Luteolin on Plasma TC and TG --- p.95 / Chapter 5.2.7 --- Luteolin Increased HDL Level and Reduced the Ratio of LDL/HDL --- p.97 / Chapter 5.2.8 --- Effect of Luteolin on Cell Cycle and Apoptotic Protein Expression --- p.99 / Chapter 5.3 --- DISCUSSION --- p.104 / CHAPTER 6 --- p.107 / cyclooxygenase inhibitors suppresse breast tumor growth in NUDE MICE --- p.107 / Chapter 6.1 --- Introduction --- p.107 / Chapter 6.2 --- Results --- p.109 / Chapter 6.2.1 --- Celecoxib and aspirin treatment had no effect on mouse body weight and liver weight --- p.109 / Chapter 6.2.2 --- Effect of celecoxib and aspirin on Xenograft Growth in Ovariectomized Mice --- p.111 / Chapter 6.2.3 --- Celecoxib and aspirin had no effect on plasma estradiol concentration --- p.113 / Chapter 6.2.4 --- Celecoxib and Aspirin Had no Effect on Uterine Weight --- p.114 / Chapter 6.2.5 --- Protein expression of COX-2, Cell cycle-related and cell Apoptotic Genes --- p.115 / Chapter 6.2.6 --- Detection of Related miRNA Expression Level in Tumors --- p.118 / Chapter 6.2.7 --- c-Myc mRNA Expression Level were Regulated in Tumors --- p.121 / Chapter 6.3 --- DISCUSSION --- p.124 / CHAPTER 7 --- p.127 / SUMMARY --- p.127 / REFERENCE --- p.131

Submitted by Gabriela Lopes (gmachadolopesufpel@gmail.com) on 2017-04-24T11:58:28Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertaçaofinalll.pdf: 1151891 bytes, checksum: 0b347b32b7f2948018d266fd346e3ed7 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2017-05-04T19:03:28Z (GMT) No. of bitstreams: 2 dissertaçaofinalll.pdf: 1151891 bytes, checksum: 0b347b32b7f2948018d266fd346e3ed7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-05-04T19:03:28Z (GMT). No. of bitstreams: 2 dissertaçaofinalll.pdf: 1151891 bytes, checksum: 0b347b32b7f2948018d266fd346e3ed7 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-03-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / O mel é um alimento natural e nutritivo, com elevado teor de carboidratos e água, contendo também quantidades menores de diversos ácidos orgânicos, enzimas, vitaminas, hormônios, flavonoides, proteínas, compostos aminados e outros elementos orgânicos e inorgânicos. Compostos fenólicos e carotenoides, mesmo estando em baixa concentração, conferem efeito anti-inflamatório, antioxidante e antimicrobiano ao produto, aumentando a imunidade e outras atividades fisiológicas do organismo. O teor e diversidade dos constituintes do mel são dependentes das condições regionais da área forrageada pelas abelhas. Assim, este trabalho teve por objetivo a determinação do perfil físico químico, de compostos bioativos e da atividade antioxidante de méis oriundos de mesorregiões do estado do Rio Grande do Sul. Para tanto, foram analisadas vinte e uma amostras de diferentes produtores do Sudoeste e Sudeste Rio-Grandense, quanto ao teor de cinzas, pH, acidez total, umidade, sólidos solúveis totais, cor, condutividade elétrica e açúcares, através de metodologias oficiais; além das avaliações de compostos fenólicos, flavonoides, carotenoides e atividade antioxidante, por espectrofotometria. Para a maioria das amostras, os parâmetros físico-químicos determinados se apresentaram dentro dos padrões brasileiros e internacionais. Os conteúdos de compostos fenólicos e de flavonoides das amostras avaliadas neste estudo reafirmam a qualidade dos méis. A análise de componentes principais permitiu agrupar amostras de acordo com sua origem geográfica, em dois grandes grupos, utilizando apenas seis parâmetros. Mesmo que a flora e as condições climáticas da zona geográfica estudada sejam semelhantes, este trabalho demonstra que pode ser possível classificar o mel por origem geográfica, o que contribuiria para conhecimento da rastreabilidade físico química deste produto. / Honey is a natural and nutritious food with a high content of carbohydrates and water, also containing smaller amounts of various organic acids, enzymes, vitamins, hormones, flavonoids, proteins, amino compounds and other organic and inorganic elements. Phenolic compounds and carotenoids, even in low concentration, confer anti-inflammatory, anti-oxidant and antimicrobial effect to the product, increasing the immunity and other physiological activities of the organism. The content and diversity of the constituents of honey are dependent on the regional conditions of the area foraged by the bees. The objective of this work was to determine the chemical physical profile, bioactive compounds and antioxidant activity of honey from mesoregions in the state of Rio Grande do Sul. Twenty one samples from different producers were analyzed of the Southwest and Southeast Rio-Grandense, as regards ash content, pH, total acidity, moisture, total soluble solids, color, electrical conductivity and sugars, through official methodologies; besides the evaluations of phenolic compounds, flavonoids, carotenoids and antioxidant activity, by spectrophotometry. For most of the samples, the physical and chemical parameters determined were within the Brazilian and International standards. The contents of phenolic compounds and flavonoids of the samples evaluated in this study reaffirm the quality of the honey. The analysis of main components allowed to group samples according to their geographical origin, in two large groups, using only six parameters. Even though the flora and climatic conditions of the geographical area studied are similar, this work demonstrates that should be possible to classify honey by geographical origin, which would contributes to the knowledge of the physical chemical traceability of this product.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / As doenças cardiovasculares são a principal causa de morte nos países ocidentais. Alguns estudos sugerem que o chá verde tem efeito benéfico sobre diferentes fatores de risco cardiovascular. No entanto, outros estudos não mostraram essa associação. Objetiva avaliar em mulheres pré-hipertensas obesas o efeito do consumo de chá verde sobre: a pressão arterial, a função endotelial, o perfil metabólico, a atividade inflamatória e a adiposidade corporal. Estudos clínico, randomizado, cruzado, duplo-cego e placebo-controlado. Durante 4 semanas as mulheres foram orientadas a ingerir 3 cápsulas de extrato de chá verde por dia (500mg extrato chá verde/cápsula) passando por 2 semanas de washout e posteriormente ingeriam por mais 4 semanas o placebo. As mulheres que iniciaram o estudo tomando placebo posteriormente utilizaram o chá verde. Ou seja, todas as pacientes receberam chá verde e placebo por um mesmo período. No início e final de cada tratamento foram analisadas as variáveis. Foram avaliadas 20 mulheres pré-hipertensas, obesidade grau I e II, idade entre 25 e 59 anos. O local do estudo foi o Laboratório da Disciplina de Fisiopatologia Clínica e Experimental Clinex. Universidade do Estado do Rio de Janeiro. As variáveis estudadas foram a pressão arterial, índice de hipertemia reativa (avaliada com Endo-PAT2000), proteína C reativa, interleucina-6, fator de necrose tumoral-α, molécula de adesão intercelular e molécula de adesão vascular celular, inibidor de ativador do plasminogênio, fator de crescimento endotelial vascular, E-selectina, adiponectina, colesterol total, LDL-colesterol, HDL-colesterol, triglicérides, glicemia, insulina, HOMA, índice de massa corporal, circunferência de cintura, circunferência de quadril, relação cintura quadril e percentual de gordura corporal. Como resultados, na avaliação da pressão arterial pela monitorização ambulatorial da pressão arterial, observou-se redução significativa da pressão arterial sistólica de 24 horas (pré 130,31,7 mmHg vs. pós 127,02,0 mmHg; p= 0,02), pressão arterial sistólica diurna (pré 134,01,7 mmHg vs. pós 130,72,0 mmHg; p= 0,04) e pressão arterial sistólica noturna (pré 122,21,8 mmHg vs. pós 118,42,2 mmHg; p= 0,02), após o consumo do chá verde, em comparação ao uso do placebo. Após o consumo do chá verde foi observado aumento, embora estatisticamente não significativo, no índice de hiperemia reativa (pré 1,980,10 vs. pós 2,220,14), além de redução expressiva na concentração da molécula de adesão intercelular (pré 91,88,0 ng/ml vs. pós 85,85,6 ng/ml) e do fator de crescimento endotelial vascular (pré 195,846,2 pg/ml vs. pós 158,638,7 pg/ml), porém sem significância estatística. As demais variáveis avaliadas não se modificaram de forma significativa após o consumo do chá verde, em comparação ao placebo. Foi observada forte correlação entre redução de pressão arterial sistólica e diastólica de 24hs, avaliada pela monitorização ambulatorial da pressão arterial, e o aumento do índice de hipertemia reativa (r= -0,47; r= -0,50, respectivamente). Os resultados do presente estudo sugerem que o chá verde tem efeito benéfico sobre a pressão arterial e possivelmente sobre a função endotelial. / Cardiovascular diseases are the leading cause of mortality in Western countries. Some studies have suggested that green tea has beneficial effects on different cardiovascular risk factors. However, others have failed to show such an association. Objective to evaluate the effects of green tea on blood pressure, endothelial function, metabolic profile, inflammatory activity and body adiposity in obese pre-hypertensive women. Study clinical, randomized, crossover, double-blinded, placebo-controlled. During 4 weeks women were instructed to ingest 3 capsules of green tea extract per day (500mg green tea extract/capsule), after 2 weeks of washout and then ingested placebo for 4 weeks. The women who began the study with placebo later have used green tea. That is, all patients received placebo and green tea for the same period. At the beginning and end of each treatment the variables were analyzed. Study of 20 women with pre-hypertension, obesity grade I and II, aged between 25 and 59 years. Study site in Laboratory of the Discipline of Clinical and Experimental Pathophysiological Clinex. Rio de Janeiro State University. Variables studied was blood pressure, reactive hyperemia index (evaluated with Endo-PAT2000), C-reactive protein, interleukin 6, tumor necrosis factor alpha, vascular cell adhesion molecule, intercellular adhesion molecule, plasminogen activator inhibitor-1, vascular endothelial growth factor, E-selectin, adiponectin, total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglycerides, blood glucose, insulin, HOMA, body mass index, waist circumference, hip circumference, waist-to-hip ratio and body fat. As results, in the assessment of blood pressure by ambulatory blood pressure monitoring was observed significant reduction in 24 hours systolic blood pressure (pre 130.31.7 mmHg vs. post 127.02.0 mmHg; p= 0.02), daytime systolic blood pressure (pre 134.01.7 mmHg vs. post 130.72.0 mmHg; p= 0.04) and nighttime systolic blood pressure (pre 122.21.8 mmHg vs. post 118.42.2 mmHg; p= 0.02), after consumption of green tea compared with placebo. After consumption of green tea, there was an increase, although not statistically significant, in reactive hyperemia index (pre 1.980.10 vs. post 2.220.14), besides expressive reduction in the concentration of intercellular adhesion molecule (pre 91.88.0 ng/ml vs. post 85.85.6 ng/ml) and vascular endothelial growth factor (pre 195.846.2 pg/ml vs. post 158.638.7 pg/ml), however without statistical significance. The other variables evaluated did not change significantly after consumption of green tea. A strong correlation was observed between reduction in 24 hours systolic blood pressure and 24 hours diastolic blood pressure, assessed by ambulatory blood pressure monitoring, and the increase of reactive hyperthermia index (r= -0.47; r= -0.50, respectively). The results of this study suggest that green tea has a beneficial effect on blood pressure and possibly on endothelial function.

Submitted by MÔNICA SOUSA CAMPOS (monicabioufg@yahoo.com.br) on 2018-05-30T18:29:47Z No. of bitstreams: 1 Campos, Mônica Sousa.pdf: 6442713 bytes, checksum: b70652123809d9c255cdb371d59e5fd2 (MD5) / Approved for entry into archive by Paula Torres Monteiro da Torres (paulatms@sjrp.unesp.br) on 2018-05-30T20:03:48Z (GMT) No. of bitstreams: 1 campo_ms_do_sjrp_int.pdf: 6442713 bytes, checksum: b70652123809d9c255cdb371d59e5fd2 (MD5) / Made available in DSpace on 2018-05-30T20:03:48Z (GMT). No. of bitstreams: 1 campo_ms_do_sjrp_int.pdf: 6442713 bytes, checksum: b70652123809d9c255cdb371d59e5fd2 (MD5) Previous issue date: 2018-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A crisina é um composto natural biologicamente ativo encontrado predominantemente em flores de maracujá azul, em mel, camomila, própolis e casca de frutas. Possui propriedades potentes como efeito anti-inflamatório, antioxidante e tem sido empregada para o tratamento de desordens reprodutivas. Essa flavona tem o potencial de aumentar os níveis de testosterona endógena, tanto por inibir a enzima aromatase, quanto por estimular a esteroidogênese testicular. Alterações no metabolismo hormonal mediadas por interferências exógenas podem interferir na fisiologia prostática resultando em modificações na atividade secretora da glândula e na regulação dos receptores hormonais. Assim, o objetivo deste estudo foi avaliar os efeitos da exposição à crisina sobre a próstata e gônadas de gerbilos adultos. Para avaliar o potencial androgênico da crisina, nós analisamos, comparativamente, os efeitos da testosterona sobre estes mesmos órgãos. Machos e fêmeas de gerbilos com 90 dias de idade foram tratados com crisina (50 mg/kg/dia) ou com cipionato de testosterona (1 mg/kg/semana) e divididos tem 3 subgrupos que foram eutanasiados após 3, 7 e 21 dias de tratamento. As próstatas foram coletadas para análises morfológicas, morfométrico-estereológicas, imuno-histoquímicas e ultraestruturais. Testículos e ovários foram submetidos a análises morfológicas e morfométrico-estereológicas. Os níveis séricos de testosterona e 17β-estradiol foram mensurados por ELISA. Machos e fêmeas tratados com crisina não apresentaram aumento dos níveis séricos de testosterona. No entanto, apenas as fêmeas tratadas com crisina durante 21 dias demonstraram aumento nos níveis séricos de estradiol. Foram observados tanto na próstata ventral masculina, quanto na próstata feminina em todos os tempos de tratamento com crisina, aumento da frequência de receptores androgênicos (AR), maior taxa de proliferação e hiperplasia glandular. Além disso, foi observada nas fêmeas em todos os tempos de exposição com crisina maior frequência imunomarcação para receptor estrogênico alfa (ERα). Ultraestruturalmente, machos e fêmeas tratados com crisina apresentaram intenso desenvolvimento das organelas da rota biossintética-secretora, acompanhada de intensa remodelação estromal, enquanto toxicidade celular foi observada apenas nas fêmeas. Nas gônadas masculinas o tratamento com crisina preservou a morfologia testicular. Em fêmeas, observou-se um maior número de folículos ovarianos em maturação. Comparativamente o tratamento com cipionato de testosterona foi capaz de causar lesões na próstata e gônadas, visto que focos de neoplasia intraepitelial prostática e degeneração gonadal foram observados em ambos os sexos. Esses resultados demonstram que a exposição à crisina, preservou a morfologia testicular normal, aumentou o número de folículos ovarianos em crescimento, aumentou a atividade secretória e alterou a regulação de receptores hormonais na próstata, potencializando a resposta desta glândula aos efeitos biológicos dos esteróides endógenos. Assim nas condições experimentais desse estudo embora a crisina e a testosterona evocassem alterações morfológicas semelhantes na próstata gerbilos masculina e feminina, a suplementação com crisina foi mais favorável à saúde da próstata. Contudo, a administração de crisina como agente fitoterápico deve ser considerada com precaução, visto que esse flavonóide parece exercer efeitos diferenciais em machos e fêmeas. / Chrysin is a naturally occurring biologically active compound found predominantly in blue passion flower, honey, chamomile, propolis and fruit peel. It has potent anti-inflammatory and antioxidant properties and has been used for the treatment of reproductive disorders. This flavone has the potential to increase endogenous testosterone levels both by inhibiting the aromatase enzyme and stimulating testicular steroidogenesis. Changes in hormone metabolism mediated by exogenous interferences may interfere with the prostatic physiology resulting in changes in the secretory activity of the gland and in the regulation of hormonal receptors. Thus, the objective of this study was to evaluate the effects of the exposure to chrysin on the prostate and gonads of adult gerbils. To evaluate the androgenic potential of chrysin, we comparatively analysed the effects of testosterone on these organs. Male and female gerbils aged 90 days were treated with either chrysin (50 mg/kg/day) or testosterone cypionate (1 mg/kg/week), subdivided into 3 subgroups and euthanized after 3, 7 and 21 days of treatment. The prostates and gonads were collected for morphological, morphometric-stereological, ultrastructural and immunehistochemical analyses. The testes and ovaries were subjected to morphological and morphometric-stereological analyses. Serum levels of testosterone and 17β-estradiol were determined using ELISA methods. Males and females treated with chrysin did not show increase in serum testosterone levels. However, only the females treated with chrysin for 21 days showed increase in the serum levels of estradiol. It was observed in both ventral prostate of males and in prostate of females in all the times of treatment with chrysin an increase in the frequency of androgen receptors (AR), a higher rate of proliferation and glandular hyperplasia. In addition, it was observed in all exposure times of females treated with chrysin a higher immunoreactivity frequency for alpha estrogen receptor (ERα). As to ultrastructure, males and females treated with chrysin showed intense development of the organelles of the biosynthetic-secretory route, accompanied by intense stromal remodeling. Cell toxicity was observed only in females. In the gonads of males the treatment with chrysin preserved testicular morphology. In females, we observed a larger number of ovarian follicles in maturation. Comparatively, the treatment with testosterone cypionate was able to cause lesions in the prostate and gonads, since the foci of prostatic intraepithelial neoplasia and gonadal degeneration were observed in both sexes. These results demonstrate that exposure to chrysin preserved normal testicular morphology, increased the number of ovarian follicles in growth, higher activity of secretory and changed the regulation of hormone receptors in the prostate potentiating the response of this gland to the biological effects of endogenous steroids. Therefore, under the experimental conditions of this study, although the chrysin and testosterone evoked similar morphological changes to those in the prostate of both sexes, supplementation with chrysin appeared to be more favorable to the prostate health. However, the chrysin intake as a phytotherapic agent should be considered with caution given that this flavonoid seems to exert distinct effects in males and females.

Le transporteur de drogues membranaire MRP1 participe à la résistance des cellules cancéreuses à la chimiothérapie lorsqu’il est surexprimé. Cette surexpression peut être exploitée afin de provoquer l’apoptose sélective de ces cellules, MRP1 devenant leur talon d’Achille : c’est l’effet de sensibilité collatérale (SC). Ainsi, le vérapamil stimule l’efflux médié par MRP1 d’un tripeptide antioxydant indispensable aux cellules, le GSH ou glutathion réduit, et provoque la mort sélective des cellules surexprimant ce transporteur. La recherche d’autres agents de SC comme le vérapamil nous a menés à l’étude de composés flavonoïdiques pouvant induire un efflux rapide et massif de GSH. Parmi ces composés, nous avons identifié un puissant agent de SC des cellules résistantes surexprimant MRP1, le dimère de flavonoïde 4e, candidat très prometteur pour de futures études in vivo. Nous avons déterminé que la surexpression de MRP1 est effectivement responsable de la SC dans les cellules cancéreuses résistantes H69AR, et que l’efflux de GSH se doit d’être massif et prolongé pour induire l’apoptose des cellules. Nous avons montré que cet efflux perturbe l’homéostasie du glutathion et l’état redox des cellules, entraînant un stress oxydatif qui participe au déclenchement de la mort cellulaire. Enfin, nous nous sommes attachés à identifier d’éventuelles cibles secondaires des agents de SC dans les cellules surexprimant MRP1, via l’initiation de l’étude de leur transcriptome et métabolome. La compréhension du mécanisme d’action de ces agents de sensibilité collatérale vise, à terme, à l’éradication des cancers résistants surexprimant MRP1 / The membrane drug transporter MRP1 is involved in the resistance of cancer cells to chemotherapy, when overexpressed. This overexpression can be exploited in order to induce the selective apoptosis of these cells, so that MRP1 becomes their Achilles’ heel: this is called Collateral Sensitivity (CS). Thus verapamil stimulates the MRP1-mediated efflux of GSH (reduced form of glutathione) that is an antioxidant tripeptide essential for cells, and induces the selective death of MRP1- overexpressing cells. Seeking for other CS agents than verapamil led to the study of flavonoid compounds able to induce a massive and rapid efflux of GSH and to the identification of a powerful CS agent of resistant cells overexpressing MRP1, i.e. flavonoid dimer 4e, which is a very promising candidate for in vivo studies. We determined that overexpression of MRP1 is indeed responsible for CS in H69AR resistant cancer cells, and that GSH efflux must be massive and protracted in order to induce cell apoptosis. We showed that this efflux disturbs glutathione homeostasis and cell redox state, which leads to an oxidative stress that is involved in triggering cell death. At last, we sought to identify possible secondary targets of CS agents in MRP1-overexpressing cells, via the initiation of transcriptomic and metabolomic studies. Understanding the mechanism of action of these Collateral Sensitivity agents aims to the eradication of resistant cancers that overexpress MRP1

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / The present work describes the chemical study of leaves, stems and roots of the Tephrosia egregia Sandwith (Fabaceae) species, through the analysis of the volatile and nonvolatile constituent of the specie. The determination of the volatile chemical composition of leaves and stems of T. egregia showed the predominance of sesquiterpenes, with some monoterpenes and trisnor-sesquiterpenes. The comparison between identified constituents in the leaves (16; 88.75%) and stems (13; 85.22%) showed a similarity between the samples, although the trisnor-sesquiterpenes geijeren and pregeijeren were the major constituents in both the essential oils. From the chromatographic investigation of the essential oil of leaves, the trisnor-sesquiterpene dictamnol was isolated for the first time in the Tephrosia genus. The chromatographic investigation of the roots of T. egregia yields pongachalcone and praecansone B, of pongaflavone, of 6a,12a-dehydrorotenone and 12a-hydroxyrotenone, the mixture of sitosterol and stigmasterol, and their glucosylated forms, and the maackiain. From its leaves were isolated p-coumaric acid and ferulic acid. This two compounds had been isolated for the first time in the genus. The assays with extracts and isolated substances of T. egregia showed that the studied specie has very important larvicidal activity against Aedes aegypti and allelopathic activity, with best result for the ethanolic extract of the roots. In other hand, the bioassays of antimicrobial activity against of S. aureaus, E. coli, P. aeruginosa, S. choleraesuis and C. albicans, and the nematicidal activity on Meloidogyne incognta not shown significant results. / O presente trabalho descreve o estudo quÃmico das folhas, talos e raÃzes de Tephrosia egregia Sandwith (Fabaceae), atravÃs da anÃlise dos constituintes volÃteis e nÃo volÃteis da espÃcie. A determinaÃÃo da composiÃÃo quÃmica volÃtil das folhas e talos de T. egregia mostrou a predominÃncia de sesquiterpenos, com relatos de monoterpenos e trisnorsesquiterpenos. A comparaÃÃo entre os constituintes identificados nas folhas (16; 88,75%) e talos (13; 85,22%) revelou semelhanÃa entre os mesmos, onde os trisnor-sesquiterpenos geijereno e o pregeijereno foram os constituintes majoritÃrios em ambos os Ãleos essenciais. A partir do fracionamento cromatogrÃfico do Ãleo essencial das folhas foi isolado o trisnorsesquiterpeno dictamnol, relatado pela primeira vez no gÃnero Tephrosia. O estudo dos constituintes nÃo volÃteis foi iniciado a partir da obtenÃÃo dos extratos etanÃlicos das folhas, talos e raÃzes da espÃcie estudada. O fracionamento cromatogrÃfico das raÃzes levou ao isolamento das chalconas pongachalcona e praecansona B, da flavona pongaflavona, dos rotenoides 6a,12a-desidrorotenona e 12a-hidroxirotenona, da mistura dos esterÃides sitosterol e estigmasterol e de suas misturas nas formas glicosiladas e do pterocarpano maackiaina. A partir do extrato acetato de etila do decocto das folhas de T. egregia foram isolados os fenilpropanÃides Ãcido p-cumÃrico e Ãcido ferÃlico, descritos pela primeira vez no gÃnero estudado. Os ensaios de atividades biolÃgicas realizados para os extratos e substÃncias isoladas de T. egregia mostraram que a espÃcie estudada apresenta atividades larvicida sobre Aedes aegypti e alelopÃtica significativas, com destaque para o extrato etanolico das raÃzes (TERES). NÃo foram encontrados resultados significativos para os bioensaios de atividade antimicrobiana sobre cepas de S. aureaus, E. coli, P. aeruginosa, S. choleraesuis e C. albicans, assim como para atividade nematicida sobre Meloidogyne incognita.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Este trabalho descreve a investigaÃÃo quÃmica de plantas dos gÃneros Abarema e Calliandra, ambas pertencentes à famÃlia Leguminosae. A prospecÃÃo quÃmica de Abarema cochliacarpos culminou no isolamento de 11 substÃncias, enquanto de Calliandra depauperata foram isolados 10 compostos. Dos extratos etanÃlicos das diversas partes de A. cochliacarpos (madeira do caule, casca do caule e folhas) foram isolados e caracterizados os esterÃides: espinasterol, 3-O-β-D-glicopiranosil-espinasterol e 3-O-β-D-(6â-O-dodecanoil)-glicopiranosil-espinasterol; a mistura dos triterpenos Ãcido oleanÃico e Ãcido ursÃlico; os flavonÃides catequina, taxifolina, miricetrina e 3â,4â,7,8-tetrahidroxiflavonol, alem do Ãcido gÃlico e galato de etila. O composto 3-O-β-D-(6â-O-dodecanoil)-glicopiranosil-espinasterol esta sendo registrado pela primeira vez. Do extrato etanÃlico das raÃzes de C. depauperata isolou-se os flavonÃides 5-metoxi-3â,4â,7-trihidroxiflavona; 3â,4â,7-trihidroxiflavona e 4â,6â,7-trimetoxi-3â-hidroxiflavona; os diterpenos de esqueletos cassano 7β,17-dihidroxi-12-oxo-cassan-13,15-dieno; 15,16-bisnor-7β,17-dihidroxi-12-oxo-cassan-13-eno e depauperatina, alem dos Ãsteres graxos: tetracosanodioato de bis-(2,3-dihidroxipropila); docosanodioato de bis-(2,3-dihidroxipropila); 24-hidroxi-tetracosanoato de 2,3-dihidroxipropila e 26-hidroxi-hexacosanoato de 2,3-dihidroxipropila. Os compostos 4â,6â,7-trimetoxi-3â-hidroxiflavona; 15,16-bisnor-7β,17-dihidroxi-12-oxo-cassan-13-eno e depauperatina, assim como todos os Ãsteres graxos estÃo sendo registrados na literatura pela primeira vez. A determinaÃÃo estrutural dos metabÃlitos secundÃrios isolados envolveu o uso de tÃcnicas espectromÃtricas como IV, EM e RMN 1H e 13C, incluindo tÃcnicas bidimensionais como COSY, HMQC, HMBC e NOESY, bem como comparaÃÃo com dados descritos na literatura. / This work describes the chemical investigation of plants from the genera Abarema and Calliandra both belonging to Leguminosae family. The chemical prospection of Abarema cochliacarpos resulted in the isolation of 11 substances while from Calliandra depauperata was isolated 10 compounds. From EtOH extracts of different parts of A. cochliacarpos (wood, wood bark and leaves) were isolated and characterizated of steroids: spinasterol, 3-O-β-D-glucopiranosyl-spinasterol and 3-O-β-D-(6â-O-dodecanoil)-glucopiranosyl-spinasterol), the mixture triterpenes oleanolic and ursolic acids; the flavonoids catechin, taxifolin, miricetrin and 3â,4â,7,8-tetrahydroxyflavonol, besides of galic acid and ethyl galate. Compound 3-O-β-D-(6â-O-dodecanoil)-glucopiranosyl-spinasterol) was isolated for the firs time. From roots EtOH extract of C. depauperata were isolated the flavonoids 5-methoxy-3â,4â,7-trihydroxyflavone; 3â,4â,7-trihydroxyflavone and 4â,6â,7-trimethoxy-3â-hydroxyflavone; the cassane diterpenes: 7β,17-dihydroxy-12-oxo-cassan-13,15-diene, 15,16-bisnor-7β,17-dihydroxy-12-oxo-cassan-13-ene and depauperatin, besides the fatty esters bis-(2,3-dihydroxypropil) tetracosanodioate, bis-(2,3-dihydroxypropil) docosanodioate, 24-hydroxy-tetracosanoate-2,3-dihydroxypropil and 26-hydroxy-hexacosanoate-2,3-dihydroxypropil. Compounds 4â,6â,7-trimethoxy-3â-hydroxyflavone; 15,16-bisnor-7β,17-dihydroxy-12-oxo-cassan-13-ene and depauperatin, and all fatty esters are being reported for the first time. The structural determination of all secondary metabolites isolated in this work involved spectrometric techniques such as: IR, MS and NMR including 2D (COSY, HMQC, HMBC e NOESY) experiments, as well as, comparison with published data

A exposição ao sol traz benefícios à saúde, no entanto, o excesso pode ocasionar danos cutâneos agudos e crônicos, dentre os quais se destacam as neoplasias. A fotoproteção é um método para a prevenção dos efeitos danosos da radiação ultravioleta (UV) e a biodiversidade Brasileira é campo fértil para as pesquisas nesta área. Dessa forma, os objetivos da presente pesquisa envolveram o desenvolvimento de formulações fotoprotetoras bioativas contendo rutina ou quercetina (compostos bioativos) e filtros solares físicos (dióxido de titânio e óxido de zinco); a caracterização das formulações por meio de ensaios físico (viscosidade aparente) e físico-químico (valor de pH); a determinação da eficácia fotoprotetora estimada por espectrofotometria de refletância difusa com esfera de integração; e a avaliação da estabilidade das preparações por meio do Teste de Estabilidade Normal (TEN). Na etapa do Desenvolvimento, a preparação composta por Dermabase® vegetal (10,0% p/p); sistema umectante (8,0% p/p); sistema emoliente (6,0% p/p); sistema quelante/antioxidante (0,6% p/p); sistema conservante (1,0% p/p); e água destilada recém destilada (74,4% p/p), foi selecionada como a formulação-base. As preparações contendo os compostos bioativos e ativos, isolados ou em associações, possuíram valores de pH biocompatíveis com o da pele, abrangendo o intervalo de 4,28 (5,0% p/p de rutina) a 7,58 (5,0% p/p de dióxido de titânio); aspecto de creme com intervalo de viscosidade aparente entre 12400 (5,0% p/p de óxido de zinco + 5,0% p/p de dióxido de titânio + 2,5% p/p de quercetina) e 31900 cP (5,0% p/p de óxido de zinco + 5,0% p/p de dióxido de titânio + 5,0% p/p de rutina); eficácia fotoprotetora estimada na faixa de fator de proteção solar (FPS) de 2,1 (2,5% p/p de quercetina) a 45,3 (5,0% p/p de óxido de zinco + 5,0% p/p de dióxido de titânio + 5,0% p/p de quercetina); e amplo espectro de proteção com valor mínimo de comprimento de onda crítico igual a 377 nm (5,0% p/p de óxido de zinco). Por meio do TEN, as preparações contendo os compostos bioativos e ativos isolados ou a associação dos filtros solares físicos se mantiveram estáveis para os parâmetros de aspecto, FPS estimado, comprimento de onda crítico, valor de pH e viscosidade aparente, nas condições de armazenamento de 22,0 ± 2,0 °C; 5,0 ± 2,0 °C - exceto para a viscosidade aparente - e 40,0 ± 2,0 °C (120 dias). As associações dos filtros físicos com os compostos bioativos se apresentaram instáveis. Apesar das respostas favoráveis que os flavonoides apreciaram, sugerirem-se que novas pesquisas poderiam ser conduzidas com a finalidade de contornar tais problemas, inclusive, realizando a comprovação da eficácia antissolar in vivo das preparações de melhor desempenho. / Exposition to sunlight promotes health benefits, however, its excess may cause acute and chronic cutaneous damages, including neoplasias. Photoprotection is a preventive approach against ultraviolet (UV) radiation deleterious effects and Brazilian biodiversity is an interesting field to the progress of researches in this science segment. The objectives of this research were the development of bioactive sunscreens containing rutin or quercetin (bioactive compounds) and inorganic UV filters (titanium dioxide and zinc oxide); the preparations\' physical (apparent viscosity) and physicochemical (pH value) characterization; the in vitro evaluation of the formulations\' photoprotective efficacy by diffuse reflectance spectrophotometry equipped with integrated sphere; and the sunscreens\' stability analysis by Normal Stability Testing (NST). The vehicle was developed with the following components: Dermabase® vegetal (10.0% w/w); humectant system (8.0% w/w); emollient system (6.0% w/w); antioxidant/chelating system (0.6% w/w); preservatives (1.0% w/w); and distilled water/aqua (74.4% w/w). Formulations containing the bioactive and the UV filters, isolated or in association, were skin biocompatible with interval of pH values from 4.28 (rutin 5.0% w/w) to 7.58 (titanium dioxide 5.0% w/w); apparent viscosity values of 12400 (zinc oxide 5.0% w/w + titanium dioxide 5.0% w/w + quercetin 2.5% w/w) to 31900 cP (zinc oxide 5.0% w/w + titanium dioxide 5.0% w/w + rutin 5.0% w/w); in vitro photoprotection activity by sun protection factor (SPF) ranging from 2.1 (quercetin 2.5% w/w) to 45.3 (zinc oxide 5.0% w/w + titanium dioxide 5.0% w/w + quercetin 5.0% w/w); and broad spectrum property with minimum critical wavelength of 377 nm (zinc oxide 5.0% w/w). By NST, sunscreens with isolated bioactive and active compounds or the UV filters\' association were considered stable during 120 days for the following parameters: aspect, in vitro SPF, critical wavelength, pH value and apparent viscosity when samples were stored at 22.0 ± 2.0 °C; 5.0 ± 2.0 °C (excluding apparent viscosity) and 40.0 ± 2.0 °C. Associations of UV filters with bioactive compounds were instable. Although the favorable results that flavonoids have achieved, it is suggested further researches aiming at to overcome the identified inconvenient, performing the in vivo SPF determination on best performance formulations to prove the estimated in vitro data.