京都大学 / 新制・課程博士 / 博士(農学) / 甲第24672号 / 農博第2555号 / 新制||農||1099(附属図書館) / 学位論文||R5||N5453(農学部図書室) / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 小川 順, 教授 井上 善晴, 教授 森 直樹 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Syftet med detta arbete var att undersöka användningen av örtmedicin vid vasomotoriska symptom i klimakteriet. Frågorna som ställdes var vilka växter som användes, vilka delar av växterna som användes, och hur växtdelarna bereddes och användes. Den sista frågeställningen tog upp hur mycket växterna lindrade de vasomotoriska symptomen. En litteraturstudie genomfördes över vetenskapliga artiklar. I artiklarna användes 20 växter, men endast fem av dessa sas lindra de vasomotoriska symptomen. De fem växterna var Actaea racemosa, Angelica sinensis, Ginkgo biloba, Glycine sp. och Pimpinella anisum.  De växtdelar som oftast användes var rötterna och dessa bereddes ofta genom extrakt som bearbetades för att öka koncentrationen och omvandlas till pulver. Pulvret formades för det mesta till tabletter och kapslar. Ibland saknades information, som vetenskapliga namn på växterna, vilka växtdelar som användes eller hur växterna bereddes. I snitt lindrade växterna de vasomotoriska symptomen med 60 %. De flesta växterna visade sig lindra milda symptom mer än starka symptom. Ett undantag var P. anisum som minskade både antal och styrkan på vallningarna med 74 %. Denna litteraturstudie visar att det finns växter som påverkar de vasomotoriska symptomen i positiv riktning. Samtidigt visar den att informationen i artiklarna ibland är bristfällig och att man inte alltid studerar om växterna kan ge biverkningar. Örtmedicin skulle kunna vara ett alternativ för kvinnor som av olika anledningar inte kan eller vill använda syntetiska hormoner eller andra farmakologiska mediciner, men för att kunna ta in örtmedicin som en del av sjukvården krävs det longitudinella studier som även studerar eventuella biverkningar eller risker för att bättre säkerställa växternas effekt på människokroppen. / The aim of this study was to investigate the use of herbal medicine for vasomotor symptoms during menopause. The questions posed were which herbs that were used, what parts of the herbs that were used, and how the plant parts were prepared and utilized. The last question covered how much the plants alleviated the vasomotor symptoms. A review of the scientific literature was carried out. In the articles, 20 herbs and plants were used, but only five of them were said to relieve the vasomotor symptoms. The five plants were Actaea racemosa, Angelica sinensis, Ginkgo biloba, Glycine sp. and Pimpinella anisum.  The most commonly used parts of the herbs were the roots, often through extracts that were processed in order to increase the concentration and to transform the plant parts into powder. The powder was then for the most part transformed to tablets and capsules. Sometimes, information was missing, such as the scientific names of the plants, what parts of the plants that were used and how the herbs were prepared and utilized. On average, the herbs alleviated the vasomotor symptoms by 60 %. Most of the herbs appeared to relieve mild symptoms more than they alleviated strong symptoms. An exception was P. anisum, which decreased both the amount of and the strength of the flushes by 74 %. This literature study shows that there are plants that influence the vasomotor symptoms in a positive direction. At the same time, it shows that the information in the articles is sometimes incomplete and that the scientists do not always study if the herbs can give side effects. Herbal medicine could be an alternative for women who, for different reasons, cannot or do not want to take synthetic hormones or other pharmacological medicines. However, in order to make herbal medicine part of the treatment offered by public health care, longitudinal studies that also investigate possible side effects or risks are needed for securing the effect of the herbs on the human body.

No description available.

Os vírus são responsáveis por infecções de distribuição mundial com elevadas prevalência e morbimortalidade sendo, muitas das vezes, sem tratamento efetivo disponível. Existem medicamentos fitoterápicos com atividade antibacteriana ou antiviral comprovadas, porém seu uso na prática clínica ainda é limitado. O objetivo deste trabalho foi investigar a presença ou ausência de atividade antiviral in vitro de extratos brutos e fracionados de Cocos nucifera L. em cultura de células Vero infectadas com herpes simplex vírus tipo 1 (HSV-1). Foram escolhidas doses não tóxicas dos extratos aquoso e hidroetanólico da fibra do C. nucifera, de 4 frações derivadas daquele com diferentes solventes (hexano, acetato de etila, metanol e água) e de duas substâncias isoladas a partir desta fibra (Substâncias CN1A e CN342B). O HSV-1 foi adicionado à cultura de células Vero uma hora após estas serem incubadas com os dois extratos e seus derivados. As placas foram analisadas em microscópio óptico a cada 24 horas, sendo o material colhido quando o efeito citopático viral no controle negativo atingisse mais de 80% das células e congelado para posterior titulação viral por TCID50. Utilizamos o aciclovir como droga de referência para o HSV-1. A substância CN342B foi capaz de inibir a replicação do HSV-1, com efeito antiviral comparável ao do aciclovir, enquanto que os extratos brutos, as quatro frações e a substância CN1A não foram efetivas. Em conclusão, a substância CN342B isolada das fibras do C. nucifera foi eficaz contra o HSV-1 in vitro / Viruses are responsible for infections worldwide with high prevalence and morbimortality, often with no effective treatment available. There are herbal medicines with proven antibacterial and antiviral activities; however, their use in clinical practice is still limited. The aim of this study was to investigate the presence or absence of in vitro antiviral activity of aqueous and hydroethanolic extracts from Cocos nucifera L. husk fiber, in culture of Vero cells infected with herpes simplex virus (HSV)-1. Non-toxic dosages of aqueous and hydroethanolic extracts, as well as the hexane, ethyl-acetate, methanol and end-aqueous fractions were used. In addition, two isolated substances (CN1A and CN342B) were tested. HSV-1 was added to the cell culture after one hour of incubation with the extracts and fractions. The plates were analyzed in optical microscopes each 24 hours, and cells were harvested when the cytopathic effect in negative controls were above 80% of the cells. The cells were then frozen for viral titulation (TCID50). Acyclovir was the reference drug for HSV-1. Substance CN342B, but none of the other drugs, was able to reduce HSV-1 replication, similarly to acyclovir. In conclusion, the substance CN342B isolated from C. nucifera husk fibers was effective against HSV-1 in vitro

Os vírus são responsáveis por infecções de distribuição mundial com elevadas prevalência e morbimortalidade sendo, muitas das vezes, sem tratamento efetivo disponível. Existem medicamentos fitoterápicos com atividade antibacteriana ou antiviral comprovadas, porém seu uso na prática clínica ainda é limitado. O objetivo deste trabalho foi investigar a presença ou ausência de atividade antiviral in vitro de extratos brutos e fracionados de Cocos nucifera L. em cultura de células Vero infectadas com herpes simplex vírus tipo 1 (HSV-1). Foram escolhidas doses não tóxicas dos extratos aquoso e hidroetanólico da fibra do C. nucifera, de 4 frações derivadas daquele com diferentes solventes (hexano, acetato de etila, metanol e água) e de duas substâncias isoladas a partir desta fibra (Substâncias CN1A e CN342B). O HSV-1 foi adicionado à cultura de células Vero uma hora após estas serem incubadas com os dois extratos e seus derivados. As placas foram analisadas em microscópio óptico a cada 24 horas, sendo o material colhido quando o efeito citopático viral no controle negativo atingisse mais de 80% das células e congelado para posterior titulação viral por TCID50. Utilizamos o aciclovir como droga de referência para o HSV-1. A substância CN342B foi capaz de inibir a replicação do HSV-1, com efeito antiviral comparável ao do aciclovir, enquanto que os extratos brutos, as quatro frações e a substância CN1A não foram efetivas. Em conclusão, a substância CN342B isolada das fibras do C. nucifera foi eficaz contra o HSV-1 in vitro / Viruses are responsible for infections worldwide with high prevalence and morbimortality, often with no effective treatment available. There are herbal medicines with proven antibacterial and antiviral activities; however, their use in clinical practice is still limited. The aim of this study was to investigate the presence or absence of in vitro antiviral activity of aqueous and hydroethanolic extracts from Cocos nucifera L. husk fiber, in culture of Vero cells infected with herpes simplex virus (HSV)-1. Non-toxic dosages of aqueous and hydroethanolic extracts, as well as the hexane, ethyl-acetate, methanol and end-aqueous fractions were used. In addition, two isolated substances (CN1A and CN342B) were tested. HSV-1 was added to the cell culture after one hour of incubation with the extracts and fractions. The plates were analyzed in optical microscopes each 24 hours, and cells were harvested when the cytopathic effect in negative controls were above 80% of the cells. The cells were then frozen for viral titulation (TCID50). Acyclovir was the reference drug for HSV-1. Substance CN342B, but none of the other drugs, was able to reduce HSV-1 replication, similarly to acyclovir. In conclusion, the substance CN342B isolated from C. nucifera husk fibers was effective against HSV-1 in vitro

No presente trabalho, realizou-se o estudo químico da fração alcaloídica total de Duguetia lanceolata St. Hil. (Annonaceae), espécie proveniente do cerrado paulista, tendo-se obtido o perfil cromatográfico e a separação decomponentes da fração alcaloídica, que resultou na obtenção do alcaloide aporfínico majoritário N-acetilanonaína, isolado da espécie, pela primeira vez. No estudo botânico de folhas, foram descritas as características da morfologia externa e interna, tendo sido ilustradas por fotografias e fotomicrografias dos itens mais importantes para a diagnose da droga caracteres xeromórficos, como: consistência coriácea, cutícula espessa, escamas e tricomas tectores estrelares nas epidermes, presença de bainhas e grandes grupos de células esclerenquimáticas freqüentes, na nervura mediana e no pecíolo. Entre outros elementos de destaque encontram-se: a distribuição de drusas na epiderme e a presença de células oleíferas dispersas no mesofilo. A avaliação da atividade antiprotozoária mostrou, de forma geral, que frente ao Plasmodium falciparum, os alcalóides totais são mais ativos sobre a cepa resistente à cloroquina (K-1) (CE50:2,0µg/mL) o que também foi observado para os mesmos componentes acetilados (CE50:3,0µg/mL). Tanto o extrato etanólico, quanto os alcaloides totais (l00µg/mL) da espécie, demonstraram elevados níveis de atividade frente às formas tripomastigotas de Tripanosoma cruzi, tendo apresentado percentual de morte de cerca de 100% e 66%, respectivamente. Este último, foi comparável ao benznidazol, fármaco usado como referência. Tais resultados são promissores tendo em vista que, os extratos não apresentaram citotoxicidade sobre as células de camundongos (RAW 264.7), até a maior concentração testada (120µg/mL). No ensaio de citotoxicidade sobre Artemia salina, os extratos etanólico e alcaloídico foram ambos inativos (DL50>1000µg/mL), em contraste com os alcalóides totais acetilados que demonstraram nível de toxicidade comparável ao do sulfato de atropina (DL50:867,60µg/mL) utilizado como referência, no ensaio. / ln this work, some chemical, botanical and pharmacological aspects of the brazilian Duguetia lanceolate St. Hil (Annonaceae) were considered. The plant specimen was collected from the cerrado biome, at São Paulo, Brazil. The isoquinoline alkaloid fraction was extracted and then acetylated. After performed the chromatographic profile, the column fractionation led to the first isolation of the major aporphine N- acetyl-anonaine from this specie. Morphological and anatomical characters of the leaves were described and illustrated by photographies and photomicrographies. Some xeromorphic characters, typical from cerrado species, were recognized: coriaceous leaves, thick cuticle, scales, stellate non-glandular trichomes, sclerenchymatic vascular sheats and scattered sclerenchymatic cell groups in the median nervure and petiole. Other important features were observed: isolated druses of calcium oxalate in each epidermal cells and oil cells scattered in the mesophyll. Evaluation of the antiprotozoal activity showed that the total alkaloid fraction (EC50:2,0µg/mL) and the same acetylated fraction (EC50:3,0µg/mL), were more active against the chloroquine resistant strain (K-1) of Plasmodium falciparum. The total acetylated alkaloids and the ethanolic extract (l00µg/mL) were highly active (0% of survival) against trypomastigotes of Tripanosoma cruzi. ln the same test, non acetylated alkaloids (l00µg/mL) killed about 66% of the parasite forms, having an activity comparable to Benznidazole, the standard drug. Those results were promising, considering the low cytoxicity showed by the plant extracts (ethanol and total alkaloid) over mice macrophages RAW 264.7, at the maximum tested concentration (120 µg/mL). The ethanol and total alkaloid extracts showed, also, low levels of citotoxicity (LD50>l000µg/mL), when assayed against the Artemia salina while the acetylated alkaloids had a LD50 value (843,2 µg/ml) comparable to the atropine sulphate.

According to WHO, leishmaniasis is endemic in 98 countries, and has been placed ninth in a global analysis of infectious diseases. Treatment of leishmaniasis is based on pentavalent antimonials but toxicity and developing resistance have been reported. Traditional medicine and scientific studies have shown that the extract of Galipea longiflora Krause (Evanta) exhibits antileishmanial activity. We hypothesized that the healing observed when using this plant might not only be due to the direct action on the parasite, but possibly to a parallel effect on the host immune response. We found that an alkaloid extract of Evanta (AEE) inhibited the growth of Leishmania braziliensis promastigotes while viability of eukaryotic cells was practically not affected. We also found that AEE interfered with polyclonal activation or Leishmania-specific re-stimulation of lymphocytes, as revealed by a reduction of in vitro cellular proliferation and IFN-g production. More important, AEE treatment of mice hosting L. braziliensis showed that AEE is able to control both inflammation and parasite load. Additionally, the healing process was improved when AEE and meglumine antimoniate were administered simultaneously. Dendritic cells (DCs) play a pivotal role in T-cell stimulation and polarization of naïve T cells. Therefore, we investigated if AEE could alter the activation of DCs and if allostimulatory DCs properties were altered if activated in the presence of AEE. DCs activated in the presence of AEE reduced the production of IL-12p40 and IL-23. When we analyzed the allostimulatory capacity of AEE-treated DCs, we found that allogeneic CD4+ T-cells secreted lower levels of IFN-γ. In conclusion, this thesis provides valuable insight into the effects of Evanta derived extract. The dual effect found for AEE, on Leishmania parasite and on the immune response, suggests that AEE may be useful in controlling the parasite burden and preventing over-production of inflammatory mediators and subsequently avoiding tissue damage. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted. Paper 3: Submitted.</p>

<p>The aim of this study was to investigate the effects of Sutherlandia frutescens on the inflammatory response and T cell differentiation in vitro using cytokines as biomarkers. Whole blood cells containing various concentrations of Sutherlandia frutescens were stimulated in vitro with either Lipopolysaccharide (LPS) or Phytohaemagglutinin (PHA). Results show that Sutherlandia frutescens is not toxic at any of the concentrations tested. The addition of Sutherlandia frutescens at high concentrations to the stimulated whole blood cell cultures reflects a significant down regulation of Interleukin(IL) 6 and IL-10 compared to the control (P&lt / 0.05) hence suppressed the inflammatory and humoral immune response. Results obtained for Inteferon-gamma (IFN ) shows that Sutherlandia frutescens is donor specific as it reflects both up and down regulation in the release of IFN at the concentrations tested. The in vitro data generated by this study supports the use of Sutherlandia frutescens in the management of inflammatory conditions and allergies such as asthma. However the effects of Sutherlandia frutescens on cell mediated immunity was found to be donor specific. Further investigation of Sutherlandia frutescens on cellular immunity is advised.</p>

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<p>The aim of this study was to investigate the effects of Sutherlandia frutescens on the inflammatory response and T cell differentiation in vitro using cytokines as biomarkers. Whole blood cells containing various concentrations of Sutherlandia frutescens were stimulated in vitro with either Lipopolysaccharide (LPS) or Phytohaemagglutinin (PHA). Results show that Sutherlandia frutescens is not toxic at any of the concentrations tested. The addition of Sutherlandia frutescens at high concentrations to the stimulated whole blood cell cultures reflects a significant down regulation of Interleukin(IL) 6 and IL-10 compared to the control (P&lt / 0.05) hence suppressed the inflammatory and humoral immune response. Results obtained for Inteferon-gamma (IFN ) shows that Sutherlandia frutescens is donor specific as it reflects both up and down regulation in the release of IFN at the concentrations tested. The in vitro data generated by this study supports the use of Sutherlandia frutescens in the management of inflammatory conditions and allergies such as asthma. However the effects of Sutherlandia frutescens on cell mediated immunity was found to be donor specific. Further investigation of Sutherlandia frutescens on cellular immunity is advised.</p>