Orientador: João Ernesto de Carvalho, Mary Ann Foglio / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-12T10:21:24Z (GMT). No. of bitstreams: 1 Vasconcellos_MariaCarolinaBayeuxLemeMontanaride_D.pdf: 13749681 bytes, checksum: 04f58739b213e3f9a71a8aac87660d56 (MD5) Previous issue date: 2008 / Resumo: Kielmeyera coriacea Mart & Zucc (Clusiacea), conhecida popularmente como PauSanto (Alves e caL, 2000), foi uma das espécies do Cerrado que apresentou atividade antiproliferativa significativa em ensaios preliminares, sendo então selecionada para este estudo. Este trabalho teve como objetivo avaliar a atividade anticâncer, isolar e identificar os princípios ativos desta espécie. O extrato bruto diclometânico obtido à quente (EBDQ) apresentou atividade antiproliferativa (in vitro), portanto foi submetido ao fracionamento cromatográfico com biomonitoramento através do teste de atividade anticâncer em cultura de células tumorais humanas. Desse fracionamento obteve-se sete frações: de F1 à F7. A fração F7 mostrou melhor atividade antiproliferativa, apresentou inibição de crescimento e morte celular para a maioria das linhagens com boa correlação entre concentração e efeito, elevada potência e seletividade para mama, próstata, ovário e ovário resistente. Na avaliação in vivo, os camundongos (balb/c) sofreram implante de fibras semipermeáveis (Hollow Fibers) contendo em seu interior linhagens tumorais humanas (Hollingshead e col.,1995). - mama, ovário resistente e ovário. Assim, o tratamento com a fração 7, reduziu a densidade celular da linhagem de mama em 61 % quando. as fibras foram implantadas no abdômem (Lp), enquanto que a doxorrubicina, a droga padrão, mostrou redução de 44%, Nas fibras subcutâneas, a Fração 7 mostrou redução de 44%, mesmo valor obtido pela doxorrubicina. No câncer de ovário, tanto a Fração 7 quanto a doxorrubicina mostraram inibição significativa apenas nas fibras intraperitoneais. Os resultados obtidos in vitro foram reproduzidos in vivo sugerindo que os princípios ativos têm condições de alcançar a circulação e chegar em diferentes locais do organismo. Com isso, a identificação dos princípios ativos responsáveis por essa atividade tomou-se fundamental. Desse modo, a fração 7 foi submetida a diversos procedimentos cromatográficos, originando três frações que foram biomonitoradas pelo teste de citotoxicidade. A Fração Beta (Fr 13) produziu inibição do crescimento e morte celular para a maioria das linhagens, com. boa correlação entre concentração e efeito com seletividade para ovário, mama e próstata. O padrão de seletividade para as linhagens que sofrem influências de esteróides sexuais foi a principal característica destas duas frações. A análise de espectro de massas (Mahato e col., 1994, 1997) sugeriu-se que a fração ß é uma mistura de triterpenos pentaciclicos de esqueleto oleânico e ursólico. Posteriormente, foi a avaliada a interferência do óxido nítrico sobre a atividade antitumoral, pois este possui atividade antitumoral dependente da concentração (Floyd e col, 2007). A fração 7 foi avaliada em cultura de mama previamente tratadas com LNAME, inibidor da enzima óxido nítrico sintetase, e LPS (Lipopolissacarídeos de E. colí), que estimula a produção de óxido nítrico. Os resultados demonstraram que a atividade foi reduzida na presença de bloqueio da síntese de NO e estimulada pelo LPS, sugerindo a participação do óxido nítrico no mecanismo de ação dos princípios ativos da fração 7. Também foi avaliado os efeitos citotóxicos dessa fração em células não-cancerígenas (fibroblastos) (Jorge e col., 2008). Dessa maneira, concluiu-se que embora tenha atividade antiproliferativa para linhagens celulares cancerígenas, não é citotóxica para células "normais". / Abstract: Kielmeyera coriacea Mart. (Clusiacea), popularly known as Pau-Santo (Alves et aI., 2000), was one of the Cerrado species that showed significant antiproliferative activity in previous tests and therefore was selected for this study. Activity guided fractionation of the crude dichloromethane extract was undertaken to isolate and identify the active compounds involved with the antiproliferative activity. Df seven fractions separated, fraction F7 presented best antiproliferative activity, showed inhibition of growth and cell death for most cell lines with good correlation between concentration and effect, high potency and selectivity for breast, prostate, ovarian and breast resistant to multipledrugs. For in vivo evaluating, mice (balb /c) had i fibers (Hollow Fibers) containing human tumor lines implanted(Hollingshead et aI., 1995) - Breast, ovarian and ovarian resistant to multiple drugs. Thus, treatment with fraction 7, reduced the cellline densitybreast by 61% when the fibers were implanted in the abdomen (ip), whereas doxorubicin, the standard drug, showed reduction by 44%. With subcutaneous fibers, Fraction 7 showed reduction by 44%,which was the same value obtained by doxorubicin. With ovarian cancer lines, both Fraction 7 and doxorubicin showed significant inhibition only on abdomen fiber. The in vitro results were reproduced by in .viv experimentso, suggesting that the active compounds are able to achieve different body locations. Fractionation of fraction by column chromatography Fr7 provided three nain fractions. The most polar of the trhee fractions, Fr f3, produced grovyth inhibition and cell death for most celllines (in vitro), with good correlation between concentration and effect with selectivity for ovarian, breast and prostate. Cell line selectivity was observed for steroidal hormone type compounds. Analysis of Fr f3 demonstrated that this fraction is a mixture of oleaonic and ursolic acid type skeletons (Mahato e col., 1994, 1997). Subsequently, nitric oxide interference was evaluated for antitumor activity (Floyd et ai, 2007). Fraction 7 previously treated with L-NAME, an inhibitor of nitric oxide synthase enzyme, LPS (Iipopolysaccharide of E. coli), which stimulates the production of nitric oxide was assessed in vitro (breast). The results demonstrated reduction of was NO synthesis and stimulated by LPS, suggesting nitric oxide to be involved with the mechanism of action. Evaluation of fraction 7 on fibroblast proliferation proved not to be very cytotoxic to "normal" cells (Jorge, 2008). / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

M.Tech. (Homoeopathy) / The purpose of this study is to determine the effect of the homoeopathic complex formula consisting of , Echinacea angustifolia tincture, Baptisia tinctoria tincture and Thuja occidentalis D1 on circulating leukocytes. These medicinal plants have immune enhancing properties and an effect on leukocytes. Leukocytes play an important role in the body's defence system. 54 volunteers participated in a randomised double blind placebo controlled trial. An initial full blood count before treatment served as a base-line control for each volunteer. A total of 15ml of the medication placebo was administered over 3 hours. After the last dose, a further three blood samples were drawn at 90 minute intervals. Blood analysis included a differential leukocyte count. The trial was conducted over a single 6 hour period. The homoeopathic medication caused a decrease in circulating leukocytes, specifically lymphocytes. The efficacy of this medicationas an immunostimulant should be confirmed on a larger study sample.

Cissampelos capensis L. f. (Menispermaceae) commonly known as “Mayisake” (Xhosa) and “Dawidjieswortel” (Afrikaans) is the most commonly used medicinal plant of the Menispermaceae family in South Africa. The rhizomes of Cissampelos capensis are the most used part of the plant to treat illnesses. This poses a threat to the ongoing conservation of this valuable endemic species. Thus, we studied the chemical variation and subsequently the bioactivity in the stems and rhizomes of Cissampelos capensis, the Eastern Cape medicinal plant, to suggest the possible use of the stems for medicinal purposes. We studied the variation in the chemical composition in the stems and the rhizomes by employing four different extraction methods; the methanolic-, non-polar-, alkaloidal- and Total Tertiary Alkaloidal (TTA) to extract compounds from Cissampelos capensis. Employing various chromatographic techniques, HPLC, NMR and LC/MS to investigate the chemical variation and the in vitro assays for the crude materials of the stems and rhizomes of Cissampelos capensis. We successfully documented a library of the phytochemicals content in Cissampelos capensis from three different regions in the Eastern Cape. We could profile different extraction methods, with the TTA extraction delivering the best comparative profile. Employing LC/MS and HPLC we identified eleven known alkaloidal compounds in the stems and rhizomes. We also isolated a known alkaloid, pronuciferine, from the TTA extract and a crystal structure of proto-quericitol from the methanolic extract, which was isolated for the first time from Cissampelos capensis. Preliminary in vitro results suggested anti-inflammatory activity in the methanolic extracts of the stems and rhizomes, while the TTA extracts showed some cytotoxicity. Finally, through analytical HPLC analysis this study found as high as 31% similarity between the chemical variation of the stems and rhizomes, but key alkaloids were not always present, indicating more work is needed before the stems can be recommended as a replacement for the rhizomes.

Diarrhea diseases remain one of the greatest health problems in many parts of the world. In some cases, the disease is mild and self-limiting; however, the symptoms may be very severe in the elderly and young children (Smith and Cheasty, 1998), as well as in immune compromised patients such as HIV/AIDS patients. The disease is one of the hallmarks of HIV/AIDS in developing countries and is also a cardinal clinical manifestation of water borne infections (Obi et al., 2007). According to a World Health Organization report (WHO, 2004), diarrhea was rated second, after respiratory infections out of the eight deadliest diseases worldwide and was responsible for 1.8 million deaths per year. This infectious disease which can cause dehydration is primarily a symptom of gastrointestinal infection, but chemical irritation of the gut or non-infectious bowel disease can also result in diarrhoe. Studies have shown that the predominant causative agents of acute and persistent diarrhoe are Gram-negative rods such as Escherichia coli, Vibrio cholerae, Aeromonas, Campylobacter, Salmonella species, Shigella species, Plesiomonas shigelloides and Yersinia enterocolitica (Obi et al., 1995, 1998, 2003; Lainson and Silva, 1999; Coker et al., 2002; Oyofo et al., 2002). Aside from bacterial agents of diarrhoea, other causative pathogens include protozoa such as Giardia lamblia and Cryptosporidium parvum; viruses such as norwalk virus and rota virus. Although fungal agents such as Candida have been shown to be prevalent in children with diarrhoe (Enweani et al. 1994), a more recent study (Forbes et al., 2001), associated higher Candida counts with recent antibiotic use. Faecal concentrations of Candida were higher in patients with diarrhoe, but the study confirmed no association between faecal candida or other yeasts and diarrhoe. Norwalk viruses, calci-like viruses and rota viruses are the major viral agents of diarrhoe. According to Parashar et al., (2006), rota virus is the leading cause of diarrhoe hospitalisation among children worldwide, causing 440,000 annual deaths in children under 5 years of age.

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

Lippia javanica is an erect, small woody shrub that grows up to two metres in height, popularly known as “fever tea” or “koorsbossie”. It is distributed throughout southern Africa covering almost the entire country of Swaziland and large parts of South Africa. Its uses range from that of caffeine free tea with fever and pain-relieving activities to treatment of microbial infections such as coughs, colds and other bronchial ailments as well as the basic symptoms of HIV and AIDS. Topical uses also include disinfection and treatment of skin disorders such as dermatitis and dry skin, and even for the treatment of lice and scabies. Furthermore, it is used in combination with Artemisia afra as a remedy against malaria and as a prophylactic against dysentery and diarrhoea. In view of the traditional medicinal importance of L. javanica, it was surprising that not much is known on the polar fraction of this plant. This work was done to explore the presence of the polar compounds of L. javanica which may contribute to the plants’ medicinal properties. The chemical screening was conducted using both the non-polar and polar extracts of the aerial parts of L. javanica collected from various localities in South Africa and Swaziland. The screening involved extraction of the aerial parts of the plant in solvents of different polarities after which TLC showed the presence of essential oils, phenolic glycosides, amino acids, diterpenoids, triterpenoids and other phenolic compounds which may include flavonoids. The chemical variation was further investigated by means of chromatographic techniques such as HPLC and GC/MS. The essential oils of L. javanica demonstrated a dramatic variation both in quality and in quantity within and between natural plant populations. The variation was found to be random and it was not correlated to the geographical distribution of this plant. The polar extracts also showed variation in the chemical compounds, v with clear differences observed between Swaziland and South African populations. Even among the amino acids a considerable variation was observed on a geographical level. Although only the aerial parts of the plants were used in each case, the observed variation could be due to the different developmental stages of the plants and the different harvesting times. We have also established that there are different compounds present in L. rehmannii (toxic Lippia species) and L. javanica which are similar to each other in appearance and they grow in the same regions and similar environments. The results demonstrated the importance of performing chemical variation studies before using these plants and for quality control purposes for marketed products. The extracts of L. javanica were subjected to the isolation of compounds and structural elucidation. Two phenylethanoid glycosides, verbascoside β-[(3,4- dihydroxyphenyl)-ethyl]-(3′-O-α-L-rhamnopyranosyl)-(4′-O-caffeoyl)-β-Dglucopyranoside and isoverbascoside β-[(3,4-dihydroxyphenyl)-ethyl]-(3′-O-α-Lrhamnopyranosyl)-( 6′-O-caffeoyl)-β-D-glucopyranoside, previously unknown in L. javanica were isolated. The structures were established by extensive spectroscopic investigation (IR, UV, FAB-MS, 1D- and 2D-NMR). The discovery of these compounds gave the most important new insight in this study and they are known to possess antioxidant activities1. This activity is still to be investigated in L. javanica. / Mrs. D. K. Olivier Dr. R. W. M. Krause

No description available.

No description available.