MSc (Chemistry) / Department of Chemistry / Malaria, an infectious disease affecting both human beings and other animals, is transmitted by parasitic protozoans belonging to the Plasmodium genus. Malaria is commonly treated with drugs such as quinine, chloroquine, and artesunate. However, the incidence of treatment failure due to drug-drug interactions and parasite resistance is increasing. Therefore, the rich medicinal potential of plants found in nature in Africa is increasingly being explored. The traditional use of Lippia javanica, Sclerocarya birrea, Melia azedarach and Capparis tomentosa for the treatment of malaria is well-known, but the phytochemistry of these four plants is not fully known. Parts of these plants were extracted and column chromatography was used to fractionate the extracts. The antioxidant activities of the fractions were determined using free radical scavenging and reducing power assays, while the cytotoxic, antiplasmodial and antitrypanosomal activities were determined using cell toxicity assay, parasite lactate dehydrogenase (pLDH) and trypanosome assay. The methanol stem bark extract of Melia azedarach (Fraction 2) had the highest phenolic content (59.39 mg GAE/g), while the methanol leaf extract of Melia azedarach had the highest flavonoid content of 188.65 mg QE/g. In the reducing power tests and DPPH free radical scavenging activity, the methanol stem bark extract of Melia azedarach had the lowest IC50 value of 0.1074 μg/mL and an IC0.5 value of 0.5296 μg/mL, respectively. Furthermore, the methanol stem bark extract of Melia azedarach at a concentration of 50 μg/mL showed significant cytotoxicity against HeLa cells (-1.22±0.07 %). The methanol stem bark extract of Melia azedarach at the tested concentration (250 μg/mL) decreased the viability of Plasmodium falciparum to 36.38±11.96 % with an IC50 value of 6.5 μg/mL. Concerning the antitrypanosomal activity, the methanol stem bark extract of Melia azedarach affected the viability of the trypanosomes at the tested concentration (250 μg/mL), giving a viability of 14.05 ± 0.59 %, with an IC50 value of 0.4 μg/mL. The presence of epicatechin (29) and catechin (31) in this extract was confirmed using several spectroscopic techniques (IR, NMR, UPLC-MS and HRMS). / NRF

Thesis (PhD)-- Macquarie University, Division of Environmental and Life Sciences, Dept. of Chemistry and Biomolecular Science. 2006. / Bibliography: p. 229-249. / Ch. 1. Introduction -- ch. 2. An ethnobotanical study with the Kamilaroi and Muruwari Aboriginal communities and relationship building -- ch. 3. Biological assay methods and optimisation -- ch. 4. Ethnopharmacological study of Eremophila sturtii -- ch. 5. Ethnopharmacological study of Exocarpos aphyllus -- ch. 6. General conclusions -- Appendices. / This study covered the documentation of first-hand medicinal plant knowledge of Aboriginal communities in northern New South Wales through the isolation and characterisation of bioactive compounds from Aboriginal medicinal plants. / Mode of access: World Wide Web. / xx, 249 p. col. ill., maps, ports

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-13T17:39:04Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) ANDRÉIA CAROLINE FERNANDES SALGUEIRO.pdf: 5179931 bytes, checksum: b1e888ee98755fdef5badebb2b78a8a0 (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2017-06-13T17:39:20Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) ANDRÉIA CAROLINE FERNANDES SALGUEIRO.pdf: 5179931 bytes, checksum: b1e888ee98755fdef5badebb2b78a8a0 (MD5) / Made available in DSpace on 2017-06-13T17:39:20Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) ANDRÉIA CAROLINE FERNANDES SALGUEIRO.pdf: 5179931 bytes, checksum: b1e888ee98755fdef5badebb2b78a8a0 (MD5) Previous issue date: 2017-02-27 / Muitas plantas são utilizadas na medicina tradicional para o tratamento do Diabetes mellitus (DM) e suas complicações. A hiperglicemia crônica no DM está intimamente associada ao aumento do estresse oxidativo. Assim, esta pesquisa teve como objetivos: i) investigar quais plantas são utilizadas na medicina tradicional por pessoas com DM na cidade de Uruguaiana/RS; ii) avaliar o potencial antidiabético, antioxidante e toxicológico de duas destas plantas in silico, in vitro e in vivo. Para isso, foi realizada uma entrevista com 105 pessoas com DM em Uruguaiana/RS, no intuito de investigar os hábitos de consumo de plantas medicinais (Manuscrito 1). Dos entrevistados, 67,6% afirmaram usar plantas medicinais. As quatro plantas mais utilizadas foram a pata-de-vaca (Bauhinia), jambolão (Syzygium jambolanum; Syzygium cumini), camomila (Matricaria recutita) e macela (Achyrocline satureioides). A infusão foi a forma de preparo mais utilizada e a frequência de consumo, em mais de 80% dos casos, foi diária. Predições in silico dos constituintes majoritários das plantas mais utilizadas mostraram a existência de provável atividade (Pa) antidiabética para alguns dos compostos analisados (Manuscrito 1). Na sequência, o potencial antidiabético, antioxidante e tóxico da Bauhinia forficata Link subsp. pruinosa (BF) foi testado in silico, in vitro e in vivo, neste último caso utilizando camundongos com hiperglicemia crônica (Manuscrito 2). Os resultados mostram que os fitoconstituintes previamente identificados na infusão de BF (quercetin 3-o-(2-rhamnosyl)rutinoside; kampferol 3-o-(2-rhamnosyl)rutinoside; quercetin-3-O-rutinoside; e kaempferol-3-O-rutinoside) apresentam alta predição in silico como antioxidantes e baixa predição como antidiabéticos e como agentes tóxicos (mutagenicidade, cardiotoxicidade e hepatotoxicidade). A predição antioxidante foi confirmada in vitro e ex vivo, sendo a BF capaz de reduzir a peroxidação lipídica e controlar os níveis de espécies reativas à diclorofluoresceína (DCF-RS) em eritrócitos de camundongos com hiperglicemia crônica. Da mesma forma, a baixa predição antidiabética foi ratificada, visto que tanto a hiperglicemia, quanto os demais sintomas clássicos do DM (poliúria, polidpsia, polifagia e perda de peso) não foram controlados pelo tratamento com a BF (Manuscrito 2). Além disso, a ação da BF sobre os danos hepáticos induzidos pela hiperglicemia foi avaliada em camundongos com DM (Artigo 1). Os resultados mostraram que os animais com DM apresentavam altos níveis de NQO-1 no pâncreas, e de DCF-RS e lipoperoxidação no fígado, assim como diminuição da atividade da catalase hepática. O tratamento com a BF foi capaz de normalizar estes parâmetros, porém não teve efeitos sobre a hiperglicemia, a hepatomegalia, as proteínas carboniladas, os tiois não-proteicos e a atividade da - aminolevulinato desidratase (Artigo 1). Adicionalmente, o potencial antidiabético, antioxidante e tóxico da Achyrocline satureioides (AS) foi testado (Artigo 2). A toxicidade foi predita in silico e avaliada in vitro no ensaio de cometa com linfócitos humanos isolados, e no ensaio de determinação da dose letal mediana (DL50) em naúplios de Artêmia salina. Os resultados mostraram que os componentes majoritários identificados na infusão de AS (quercetina, isoquercitrina e ácido cafeíco) apresentam alta predição como antioxidantes e baixa predição de toxicidade, exceto para a quercetina. A ação antioxidante foi confirmada tanto para o extrato aquoso bruto (infusão), quanto para os constituintes isolados. A DL50 determinada classifica a planta como não tóxica. No ensaio de cometa não foi identificado potencial genotóxico para a infusão de AS (Artigo 2). Os dados apresentados confirmam o elevado uso de plantas por pessoas com DM na medicina tradicional. Da mesma forma, as análises realizadas apontam o estresse oxidativo como sendo um dos mecanismos envolvidos nos danos teciduais decorrentes do DM. As análises mostram ainda que os efeitos protetores resultantes do tratamento com a BF podem ser atribuídos à sua capacidade antioxidante, demonstrada in vitro e ex vivo, visto que não foi identificado potencial antidiabético in silico e in vivo. Nesta mesma linha, o alto potencial antioxidante e baixa predição toxicológica apontam a AS como uma alternativa para o tratamento dos danos causados pelo estresse oxidativo. Em suma, os resultados aqui apresentados permitem concluir que a planta BF, utilizada na medicina tradicional para tratar DM e suas complicações, não apresenta efeito antidiabético direto na forma como foi aqui testada. No entanto, sua importante atividade antioxidante faz, tanto da BF quanto da AS, potenciais agentes para o tratamento complementar do DM, especialmente considerando as complicações diabéticas decorrentes do incremento do estresse oxidativo. Neste contexto, abrem-se perspectivas para investigações futuras do uso dessas plantas como terapia complementar ao tratamento clínico tradicional. / Medicinal plants are extensively used in traditional medicine to treat Diabetes mellitus (DM) and its complications. Chronic hyperglycemia in DM is pointed as responsible for oxidative stress development. The aims of this study were: i) to evaluate which plants are used in traditional medicine by people with DM in Uruguaiana/RS; ii) to evaluate the antidiabetic, antioxidant and toxicological potential for two of these plants in silico, in vitro e in vivo. For this, a research with 105 DM patients from Uruguaiana/RS was conducted to investigate their medicinal plants consumption habits (Manuscript 1). From the interviewed people, 67.6% say they do use medicinal plants. The four more used plants were “cow paw” (Bauhinia), jambolan (Syzygium jambolanum; Syzygium cumini), chamomile (Matricaria recutita), and macela (Achyrocline satureioides). The most used form of consumption was the infusion; in more than 80% of the cases, the consumption frequency was daily. Predictions in silico for the major phytoconstituents of the most used plants showed that some compounds presented probable antidiabetic activity (Manuscript 1). In sequence, the antidiabetic, antioxidant and toxicological potential of Bauhinia forficata Link subsp. pruinosa (BF) was tested in silico, in vitro and in vivo, in the last case using mice with chronic hyperglycemia (Manuscript 2). Results show that the phytoconstituents previously identified in the BF infusion (quercetin3-o-(2-rhammosyl)rutinoside; kampferol 3-o-(2-rhammnosyl)rutinoside; quercentin-3-O-rutinoside; and kaempferol-3-o-rutinoside) show high prediction in silico as antioxidants and low prediction as antidiabetic agents and toxic agents (mutagenicity, cardiotoxicity and hepatotoxicity). The antioxidant prediction was confirmed in vivo and ex vivo. BF was able to reduce lipid peroxidation and to control the reactive dichlorofluroscein species (DCF-RS) levels in erythrocytes from hyperglycemic mice. In the same way, the low antidiabetic prediction was ratified, since both hyperglycemia and other classic DM symptoms (polyuria, polydipsia, polyphagia, and weight loss) were not controlled by BF treatment (Manuscript 2). Besides, the BF action in the hepatic damages induced by hyperglycemia was evaluated in mice with DM (Article 1). Diabetic mice showed high levels of NQO-1 in pancreas, and of DCF-RS and lipid peroxidation in the liver, as well as decrease in the activity of hepatic catalase. BF treatment was able of normalizing these parameters. However, it did not have any effects over hyperglycemia, hepatomegaly, carbonylated proteins, non-protein thiols, and the - aminolevulinate dehydratase activity (Article 1). Additionally, the antidiabetic, antioxidant, and toxicological potential of Achyrocline satureioides (AS) was tested (Article 2). The toxicity was predicted in silico and, after, evaluated in vitro with the comet assay using human lymphocytes. The median lethal dose (LD50) was evaluated in nauplii of Artemia salina. Results showed that the AS major compounds (quercetin, isoquercitrin, and caffeic acid) presents high prediction as antioxidants and low toxicity prediction, except for quercetin. The antioxidant activity was confirmed both in crude aqueous extract (infusion) and in isolated compounds. The determined LD50 classifies the plant as non-toxic. The comet assay showed no genotoxic potential for AS infusion (Article 2). Our data confirm the extensive use of plants by people with DM. In the same way, our analysis point oxidative stress as one of the mechanisms involved in tissue damages resulting of DM. The analysis also showed that the protective effects resulting of the BF treatment could be assigned to its antioxidant capacity, demonstrated in vitro and ex vivo, since no antidiabetic potential was identified in silico and in vivo. In the same line, the high antioxidant potential and the low toxicological prediction, point AS as a possible alternative treatment to the damage caused by oxidative stress. In summary, the results here presented allow us to conclude that BF plant, used in traditional medicine to treat DM and its complications, does not show direct antidiabetic effects. However, the antioxidant potential observed in both, BF and AS, make them possible complementary treatments to DM, especially considering the diabetic complications resulting of the oxidative stress increase. In this context, perspectives to future investigations on the use of these plants as complementary therapy to the traditional clinic treatment are open.

This thesis investigated the phytochemistry and pharmacology of immunomodulatory medicinal plant species used traditionally by the Q’eqchi’ Maya Healers Association (QMHA) of Belize, and the Cree of Eeyou Istchee (CEI) of northern Quebec. Using quantitative ethnobotanical methodology, we identified 107 plant species belonging to 49 families used by Q’eqchi’ healers in the treatment of symptoms from 14 usage categories related to inflammation. Regression analysis revealed that the Piperaceae, Araceae, and Begoniaceae are preferentially selected by the Maya. Healer consensus for plant species was high, with 56 species (52%) being used by all the healers, and consensus for usage categories was also high, as informant consensus factor (FIC) values for each category were greater than 0.4. Fifty-two Belizean species were evaluated for their TNF-α inhibitory activity in an LPS-stimulated THP-1 monocyte model. Twenty-one species (40%) demonstrated significant TNF-α inhibition when assayed at 100 µg/mL, 8 of which had greater than 50% of the activity of the parthenolide positive control (10 µg/mL). Significant regressions were found between the anti-inflammatory activity and total healer frequency of use (Fuse) and the use reports for 3 usage categories, which indicated that ethnobotanical parameters can in part predict the activity of traditionally used species. Five sesquiterpene lactones were isolated from the leaves of Neurolaena lobata, one of the most active species tested, all of which demonstrated anti-inflammatory activity greater than that of parthenolide (IC50 = 4.79 µM), with IC50s ranging from 0.17-2.32 µM. Lobatin B was the most active isolate tested. Ethanolic and water extracts of 17 species used by Cree healers were evaluated for their immunomodulatory activity. In general, the average anti-inflammatory activity of ethanolic extracts was 1.8 times greater than that of water extracts, and the pro-inflammatory activity of water extracts was 3.7 times greater than ethanolic extracts. Picea mariana and Pinus banksiana were the most anti-inflammatory ethanolic and water extracts, while the water extract of Sarracenia purpurea was the most pro-inflammatory. Picea marina cones, the most anti-inflammatory Cree medicine, were subjected to bioassay guided isolation. This led to the isolation of the anti-inflammatory lignan (+)-lariciresinol-9’-p-coumarate, which had an IC50 of 28.4 µM. Together, these results validate the traditional knowledge shared by our Q’eqchi’ and Cree collaborators, and draw attention to the therapeutic potential of subtropical and boreal plants as culturally appropriate complements to modern medicine. - Cette thèse porte sur la phytochimie et la pharmacologie des espèces de plantes médicinales immunomodulatrices utilisées traditionnellement par le Q’eqchi’ Maya Healers Association (QMHA) du Belize, et les Cris d'Eeyou Istchee (CEI) du nord du Québec. En utilisant une méthodologie ethnobotanique quantitative, nous avons identifié 107 espèces végétales appartenant à 49 familles utilisées par les guérisseurs Q'eqchi’ dans le traitement de symptômes appartenant à 14 catégories d'utilisation liées à l'inflammation. Une analyse de régression a révélé que les familles Piperaceae, Araceae, et Begoniaceae sont préférentiellement choisis par les Mayas. Le consensus entre guérisseurs pour les espèces végétales était élevé, avec 56 espèces (52%) étant utilisés par tous les guérisseurs, et le consensus pour les catégories d'utilisation était également élevé, car les valeurs de facteur de consensus des informants (FIC) pour chaque catégorie étaient supérieurs à 0,4. Cinquante-deux espèces du Belize ont été évaluées pour leur activité inhibitrice de TNF-α dans un modèle de THP-1 monocytes stimulés par le LPS. Vingt-et-une espèces (40%) ont montré une inhibition significative de TNF-α lorsque dosés à 100 µg/mL, dont 8 d’entre elles ont démontrées plus de 50% de l'activité du contrôle positif parthénolide (10 µg/mL). Des régressions significatives ont été observées entre l'activité anti-inflammatoire et la fréquence d'utilisation de guérisseurs totale (Fuse) et les rapports d'utilisation pour 3 catégories d'utilisation, ce qui indique que les paramètres ethnobotaniques peuvent en partie prédire l'activité des espèces traditionnellement utilisées. Cinq lactones sesquiterpéniques ont été isolés à partir des feuilles de Neurolaena lobata, l'une des espèces les plus actives testées, qui a démontré une activité anti-inflammatoire supérieure à celle du parthénolide (CI50 = 4,79 µM), avec des CI50 allant de 0,17 à 2,32 µM. Lobatin B était l’isolât le plus actif testé. Des extraits éthanoliques et aqueux de 17 espèces utilisées par les guérisseurs Cris ont été évalués pour leur activité immunomodulatrice. En général, l'activité anti-inflammatoire moyenne des extraits éthanoliques était 1,8 fois supérieure à celle des extraits d'eau, et l'activité pro-inflammatoire des extraits d'eau était de 3,7 fois supérieure à celle des extraits éthanoliques. Picea mariana et Pinus banksiana étaient les extraits éthanoliques et aqueux avec le plus d’activité anti-inflammatoire, tandis que l'extrait aqueux de Sarracenia purpurea était le plus pro-inflammatoire. Le cône de Picea marina, le médicament traditionnelle Cris le plus anti-inflammatoire, a été soumis à une isolation guidée par essais biologiques. Cela a mené à l'isolement du lignane anti-inflammatoire (+)-lariciresinol-9'-p-coumarate, qui avait une CI50 de 28,4 µM. Ensemble, ces résultats valident les connaissances traditionnelles partagées par nos collaborateurs Q'eqchi' et Cris, et mettent en évidence le potentiel thérapeutique des plantes subtropicales et boréales comme des compléments à la médecine moderne qui sont culturellement appropriées.

Spices are of great importance in the indigenous culinary and traditional medicine systems of the people of Nkonkobe Municipality of the Eastern Cape, South Africa. The present investigation evaluated the ethnopharmacological potentials of two indigenous South African spices- Foeniculum vulgare and Lippia javanica. The pharmacological investigations on these two plant species include ultra-morphology, nutrient and mineral analysis, evaluation of the essential oil, phytochemical and antioxidant assays, antimicrobial, anti-inflammatory as well as anti-urolithiatic assay of the acetone and aqueous extracts of the two plants. The species were selected for study as the most cited plants after an ethnobotanical survey conducted on the indigenous knowledge of plants used as spices and medicine in Nkonkobe Municipality, Eastern Cape of South Africa. Among the plants cited Foeniculum vulgare(Apiaceae) and Lippia javanica (Verbenaceae) stood out as the most commonly used spices. Others were members of the families; Solanaceae, Apiaceae, Amaryllidaceae, Amaranthaceae and Lamiaceae. Ultra-morphological studies conducted on the leaves of the two selected plants using scanning electron microscope revealed the presence of non-glandular and glandular trichomes, stomata and crystals. The leaf surfaces of these herbs may serve as secretory sites where aromatic secondary metabolites are produced. Analyses of the proximate, mineral, vitamin and anti-nutrients contents of these two spices showed that both species are good sources of these phytochemicals and may be used to enrich the human diet. Lippia javanica possesses lower lipid (0.50 percent), fibre (5 percent) and carbohydrate (64.96 percent) contents than Foeniculum vulgare. On the other hand, protein (20.54 percent), ash (11.60 percent) and moisture content (11.69 percent) were higher in Foeniculum vulgare than in Lippia javanica. Foeniculum vulgare showed higher N (3286 mg/100g), Mg (386.7 mg/100g), K (3187 mg/100g) and Na (1383 mg/100g) content while Lippia javanica was higher in Ca (1833 mg/100g), Zn (4.7 mg/100g), Cu (0.9 mg/100g) and Fe (78.4 mg/100g). Vitamins Aand E were also higher in Lippia javanica (1.31 mg/100g; 2.52 mg/100g) while Foeniculum vulgare (0.45 mg/100g) had higher vitamin C content. No significant differences were observed in the phytate, oxalate and tannin contents of the two spices, but saponin and cyanide were significantly lower in Lippia javanica (268.5 mg/100g; 8.45 mg/100g) than in Foeniculum vulgare (1855 mg/100g; 10.5 mg/100g) Evaluation of the essential oil component, cytotoxicity and antimicrobial activities of both fresh and dried leaves of Lippia javanica and Foeniculum vulgare revealed that the dried samples yielded more oil and also contain more chemical than the fresh samples of both plants. The overall antimicrobial activity evaluated using susceptibility and microdilution assays revealed that the oils of F. vulgare and L. javanica exhibited high antifungal and antibacterial activity, compared to the reference drugs. In addition, essential oil from fresh leaves of both spices was less toxic compared to the oil from the dried leaves. Polyphenolic evaluation of the aqueous and acetone extracts of the plants revealed that the acetone extract had higher phenol, flavanol, flavonoid and proanthocyanidin contents than the aqueous extracts. The total phenolic content of acetone and aqueous extracts were 4.49 ± 0.411 mg/g and 3.73 ± 0.498 mg/g tannic acid equivalent (TAE) respectively for Lippia javanica. The same trend was also observed in Foeniculum vulgare with total phenolic content of acetone and aqueous extracts were 4.22 ± 0.325 mg/g and 4.17 ± 0.651 mg/g tannic acid equivalent (TAE) respectively. Further assessment of the antioxidant activity of the solvent extracts revealed that both plants exhibited promising free radical scavenging potentials against 1,1 diphenyl-2-picrylhydrazyl (DPPH), 2, 2’-azino-bis(3- ethylbenzthiazoline-6-sulfonic acid (ABTS), reducing power, lipid peroxidation, nitric oxide, phosphomolybdate and hydrogen peroxide. Antimicrobial activities of the acetone and aqueous extracts of the two plants revealed moderate antibacterial and antifungal activities. They inhibited the growth of Microsporium canis and Trichophyton rubrum that were not susceptible to the standard antifungal drug used as control.

Orientador: Alba Regina Monteiro Souza Brito / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T11:51:38Z (GMT). No. of bitstreams: 1 Oliveira_PatriciadeSousa_M.pdf: 1680821 bytes, checksum: 0caf3a9ff2ee0e3612c918b4463f76da (MD5) Previous issue date: 2010 / Resumo: A Etnofarmacologia é uma ciência multidisciplinar que estuda a diversidade biológica e cultural através do uso das plantas no tratamento de doenças; junto à Etnobotânica, estuda ainda a relação entre o homem e a flora, procurando esclarecer como a cultura compreende, interpreta e se relaciona às plantas em seu ambiente. O grupo do Laboratório de Produtos Naturais, do IB da Unicamp, tem se dedicado à pesquisa de compostos vegetais com potencial atividade medicinal, selecionados através da etnofarmacologia. Partindo do interesse do grupo em dialogar com a comunidade e a possibilidade de contribuir para a valorização das diferentes formas de conhecimento, os objetivos deste trabalho foram: i) realizar estudo etnofarmacológico de espécies utilizadas como medicinais pela comunidade rural "Assentamento XX de Novembro", localizada no município de Cordeirópolis-SP; ii) avaliar o modo de gerir saúde e doença em relação aos conhecimentos médicos tradicional e moderno na comunidade; e iii) propor trabalho educativo para uso terapêutico seguro e eficaz da plantas. A pesquisa baseou-se em métodos antropológicos e observação participante, através de entrevistas com 30 informantes não-especialistas da comunidade. As plantas medicinais citadas (105 espécies) pertencem a 43 famílias, dentre as quais Asteraceae e Lamiaceae foram as mais recorrentes. As espécies utilizadas são, em geral, cultivadas e obtidas do próprio quintal ou de vizinhos; aquelas cultivadas para alimentação são bastante empregadas no tratamento de doenças. Plantas medicinais são bastante utilizadas no tratamento de doenças respiratórias e digestivas, sendo que a forma mais utilizada no preparo de remédios é o chá. A transmissão de saberes sobre uso terapêutico das plantas é feita oralmente e, na maior parte das vezes, por mulheres. Foi possível constatar que sistemas de saúde tradicional e o biomédico coexistem no cuidado familiar à saúde e que a comunidade rural é um ambiente tradicional quanto ao universo de práticas e saberes acumulados e transmitidos oralmente, mas nem por isso deixa de receber influências, cada vez mais fortes, da sociedade urbano-industrial. Os novos saberes não substituem os antigos, mas dialogam com eles produzindo outros. Dificuldades inerentes aos processos de educação informal, possível somente diante da disponibilidade dos seus agentes, também foram vivenciadas. Etnofarmacologia e Educação podem aliar-se para aproximar conhecimento popular e científico, de forma a integrar conhecimentos e possibilitar autonomia de uma dada comunidade quando preserva, questiona e renova conceitos e práticas, o que culmina na melhora de sua qualidade de vida. / Abstract: The Ethnopharmacology is a science that studies the biological and cultural diversity through the use of plants to treat diseases; together with the ethnobotany, is also considering the relationship between man and plants, seeking to clarify how the culture understands, interprets and connect with plants in your environment. The group of the Laboratory of Natural Products, IB Unicamp, has been dedicated to the research of plant compounds with potential medicinal activity, selected by the Ethnopharmacology. Based on the interest of the group about dialogue with the community and contribute to the promotion of different forms of knowledge, the objectives of this study were: i) perform Ethnopharmacological study of species used in traditional medicine by rural community called "Assentamento XX de Novembro" located in Cordeirópolis city - Brazil; ii) assess how to manage health and disease in relation to traditional medical knowledge and modern community; and iii) propose educational work for therapeutic use safe and effective of the plants. The research was based on anthropological methods and participant observation, through interviews with 30 non-specialist informants? community. Medicinal plants cited (105 species) belong to 43 families, among which Asteraceae and Lamiaceae were the most frequent. The species used are generally obtained from cultured own backyard or neighbors, those cultivate for food are often employed in the treatment of diseases. Medicinal plants are widely used in the treatment of respiratory and digestive diseases and tea is the most used in the preparation of remedies. The transmission of knowledge about therapeutic use of plants is made orally, and in most cases, by women. It was establish that traditional health systems and biomedical coexist in family health care and the rural community is a traditional as the universe of practices and knowledge accumulated and passed orally, but no longer receives influences increasingly strong of urban-industrial society. The new knowledge does not replace the old, but dialogue with them producing others. Difficulties inherent in the processes of informal education is possible only on the availability of its agents, were also experienced. Ethnopharmacology and Education can combine to bring popular and scientific knowledge in order to integrate knowledge and enable the autonomy of a given community while preserving, questions and renew concepts and practices, which culminates in improving their quality of life. / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

Made available in DSpace on 2016-08-16T18:18:40Z (GMT). No. of bitstreams: 1 TESE DE MONICA VIRGINIA VIEGAS LIMA.pdf: 3470227 bytes, checksum: 3f31c4cece76460417d5f04acc93728f (MD5) Previous issue date: 2012-12-18 / FUNDAÇÃO DE AMPARO À PESQUISA E AO DESENVOLVIMENTO CIENTIFICO E TECNOLÓGICO DO MARANHÃO / Saliva is a useful biological fluid with potential for diagnosis and monitoring of systemic disease because it reflects states of health and disease. Our objective was to evaluate the immunological and biochemical changes in saliva of pediatric patients with cancer, in diabetic patients and to investigate which plant species are most frequently used by diabetics as hypoglycemic. In immunological and biochemical evaluations Cancer patients consisted of 32 children with cancer and 115 children without cancer and the diabetic sample consisted 93 diabetic patients and 49 non diabetic. To assess the ethnopharmacological data 107 diabetics were interviewed using a standard questionnaire and semi-structured interview. The salivary biochemistry was determined by colorimetric assays and The IgA concentration was determined by Enzyme-Linked Immunosorbent Assay - ELISA. DMFT index was employed n dental evaluation. Children with cancer showed an increase in alkaline phosphatase, T4, TSH and glucose and decreased insulin and total IgA. Glucose, urea, calcium, total IgA, IgA anti-mutans IgA anti-insulin and DMFT index was higher in diabetic patients. 16 plant species have been reported for the treatment of diabetes, and pata de vaca , sweet olive, tamarind and insulin were the most used. We conclude the plant species most frequently mentioned have its efficacy as hypoglycemic scientifically attested and saliva can be used to monitor diabetics and cancer patients, which casts new perspectives in the monitoring and treatment of patients with hyperglycemic diseases. / A saliva é um fluido biológico que vem sendo utilizado na avaliação de doenças sistêmicas, pois reflete estados de saúde e doença. Investigamos as principais alterações imunológicas e bioquímicas na saliva em pediátricos com neoplasias, em pacientes diabéticos e ainda as espécies vegetais mais utilizadas pelos diabéticos como hipoglicemiantes. Foram avaliados 2 crianças com neoplasias e 115 crianças sem neoplasia e 93 pacientes diabéticos e 49 não diabéticos. Na avaliação etnofarmacológica foram entrevistados 107 diabéticos quanto ao uso de plantas no tratamento da diabetes e sintomas associados, utilizando-se questionário padrão e entrevista semi-estruturada. A bioquímica salivar foi determinada por método colorimétrico e a produção de anticorpos IgA foi determinada por ensaio imunoenzimático - ELISA. Na avaliação odontológica utilizou-se o índice CPO-D. Crianças com neoplasias apresentaram aumento na concentração de fosfatase alcalina, T4, TSH e glicose e uma diminuição de insulina e IgA total. Glicose, uréia, cálcio, IgA total, IgA anti-mutans, IgA anti-insulina e o índice CPO-D foram maiores em pacientes diabéticos. Foram relatadas 16 espécies vegetais para tratamento do diabetes, sendo que pata de vaca, azeitona doce, insulina e tamarindo foram as mais utilizadas. Concluímos que as espécies vegetais mais frequentemente mencionadas como coadjuvantes no tratamento da diabetes apresentam eficácia cientificamente comprovada como hipoglicemiantes, e ainda que a saliva pode ser utilizados no acompanhamento de diabéticos e crianças com neoplasias e o que lança novas perspectivas no acompanhamento e no tratamento de pacientes com doenças hiperglicemiantes.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-11-06T14:42:48Z No. of bitstreams: 1 juceliabarbosadasilva.pdf: 5387573 bytes, checksum: d7ba864889d911413adaa37b47b0dba9 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-11-09T14:20:59Z (GMT) No. of bitstreams: 1 juceliabarbosadasilva.pdf: 5387573 bytes, checksum: d7ba864889d911413adaa37b47b0dba9 (MD5) / Made available in DSpace on 2017-11-09T14:20:59Z (GMT). No. of bitstreams: 1 juceliabarbosadasilva.pdf: 5387573 bytes, checksum: d7ba864889d911413adaa37b47b0dba9 (MD5) Previous issue date: 2017-08-01 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / A espécie vegetal Vernonia Condensata Baker (Asteraceae), tradicionalmente empregada para o alívio de diversas doenças, tais como distúrbios gástricos e hepáticos, e, ainda, em processos inflamatórios, foi foco deste estudo que buscou aprofundar os conhecimentos sobre o potencial biológico desta espécie. As folhas da mesma foram submetidas à extração a frio com etanol. O extrato (EE) assim obtido foi seco e ressuspendido, passando por um processo de partição líquidolíquido com solventes em ordem crescente de polaridade, originando as partições: hexânica (PH), diclorometânica (PD) e em acetato de etila (PA). A atividade hepatoprotetora foi avaliada in vivo. Para tal foram aplicados três modelos de indução de lesão hepática: paracetamol dose aguda, paracetamol doses repetidas e etanol dose aguda. Para o primeiro modelo foram testados o extrato etanólico e suas partições, observou-se inibição do dano hepático para os animais tratados com PA nas concentrações 50, 100 e 200 mg / kg, com a diminuição dos níveis das transaminases hepáticas, dos parâmetros lipídicos e ação antioxidante observada pelos ensaios de peroxidação lipídica e atividade das enzimas catalase e glutationa reduzida realizados no tecido hepático. Para o modelo de paracetamol em doses repetidas os animais foram tratados com PA nas concentrações 100 e 200 mg / kg, dado o perfil do tratamento não foram observadas diferenças significativas entre os parâmetros bioquímicos dos diferentes grupos, porém foi possível verificar a atividade antioxidante da partição para este modelo. Para indução de lesão hepática aguda por etanol, observaram-se diferenças significativas para os níveis de transaminases hepáticas para os grupos tratados simultaneamente e após a indução com PA na concentração de 200 mg / kg. A atividade anti-inflamatória in vitro também foi testada frente a células RAW (macrófagos) para PA e os níveis de NO, IL- 6 e TNF- α foram dosados e observou-se redução significativa destes mediadores pró-inflamatórios. A atividade antibacteriana das amostras foi verificada pelos testes de concentração inibitória mínima (CIM), concentração bactericida mínima (CBM), checkerboard, análise da curva de crescimento, viabilidade celular e inibição da adesão do biofilme. Os resultados da CIM para PA indicaram moderada atividade antibacteriana para as cepas de S. aureus com resultados iguais ou inferiores a 625 µg / mL, apresentando, então, atividade bacteriostática. PA levou a diminuição da velocidade de crescimento das cepas de S. aureus bem como inibiu a adesão do biofilme. Em PA, que se mostrou mais promissora pelos ensaios realizados, foram identificados e quantificados por meio de cromatografia líquida de alta eficiência acoplada a arranjo de diodo com padrões externos os flavonoides luteolina, apigenina e o composto fenólico ácido clorogênico. PA foi ainda fracionado e de uma das frações obtidas foi isolado, identificado e quantificado o ácido 1,5 – o- dicafeoilquínico. A presença destes pode justificar, em parte, as atividades observadas neste estudo. / Vernonia Condensata Baker (Asteraceae), traditionally used for the relief of several diseases, such as gastric and hepatic disorders, and also in inflammatory processes, was the focus of this study, which sought to deepen the knowledge about the biological potential of this species. The leaves were subjected to cold extraction with ethanol. The extract (EE) thus obtained was dried and resuspended, passing through a liquid-liquid partitioning process with solvents in increasing order of polarity, giving the partitions: hexane (PH), dichloromethane (PD) and ethyl acetate (PA). Hepatoprotective activity was evaluated in vivo. Three models of hepatic injury induction were applied: acetaminophen, acetaminophen, acetaminophen, acetaminophen and acetaminophen. For the first model the ethanolic extract and its partitions were tested, inhibition of hepatic damage was observed for the animals treated with PA at the concentrations 50, 100 and 200 mg / kg, with the reduction of hepatic transaminases levels, lipid parameters and antioxidant action observed by the lipid peroxidation assays and the activity of catalase and reduced glutathione enzymes performed in hepatic tissue. For the paracetamol model in repeated doses the animals were treated with PA at concentrations 100 and 200 mg / kg, given the treatment profile no significant differences were observed between the biochemical parameters of the different groups, however it was possible to verify the antioxidant activity of the partition for this model. For induction of acute hepatic injury by ethanol, significant differences were observed for hepatic transaminase levels for the groups treated simultaneously and after induction with BP at the concentration of 200 mg / kg. In vitro anti-inflammatory activity was also tested against RAW (macrophages) PA cells and levels of NO, IL-6 and TNF-α were measured and a significant reduction of these pro-inflammatory mediators was observed. The antibacterial activity of the samples was verified by tests of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), checkerboard, growth curve analysis, cell viability and inhibition of biofilm adhesion. The results of CIM for PA indicated moderate antibacterial activity for S. aureus strains with results equal to or less than 625 μg / mL, presenting bacteriostatic activity. PA led to a decrease in the growth rate of S. aureus strains as well as to inhibit biofilm adhesion. In PA, which was more promising for the tests performed, the flavonoids luteolin, apigenin and the chlorogenic acid phenolic compound were identified and quantified by means of high performance liquid chromatography coupled to diode array with external standards. PA was further fractionated and one of the fractions obtained was isolated, identified and quantified 1,5 - o - dicyclohexylic acid. The presence of these may justify, in part, the activities observed in this study.

Le travail présenté dans ce manuscrit porte sur l’isolation de métabolites secondaires de plantes utilisées en médecine traditionnelle au Mali. Après avoir réalisé une enquête ethnopharmacologique, mis en parallèle avec la littérature, trois plantes ont été sélectionnées pour être étudiées : Cassia sieberiana DC., Vitex madiensis Oliv. et Pericopsis laxiflora (Benth.) Meeuwen. L’activité analgésique des extraits aqueux et méthanoliques de ces plantes ont été évaluées. Les résultats nous ont mené à conduire un fractionnement bio-guidé des extraits méthanoliques de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen. Huit composés ont été isolés à partir de fractions de l’extrait méthanolique de Cassia sieberiana DC., parmi lesquels quatre nouvelles molécules et trois nouveaux stéréoisomères ont été identifiés. Onze composés ont été isolés à partir de fractions de l’extrait méthanolique de Pericopsis laxiflora (Benth.) Meeuwen. Ce travail de recherche a permis d’approfondir nos connaissances sur la composition chimique de Cassia sieberiana DC. et de Pericopsis laxiflora (Benth.) Meeuwen et leur potentielle activité antalgique. / The present work deals with the isolation of analgesic secondary metabolites from plants used in traditional medicine in Mali. After conducting an ethnopharmacological study and comparing it with the literature, three plants were selected to be studied: Cassia sieberiana DC., Vitex madiensis Oliv. And Pericopsis laxiflora (Benth.) Meeuwen. The analgesic activity of their aqueous and methanolic extracts were screened. Results lead us to realise a bioguided partitionning on the methanolic extracts of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen. Eight coumpounds were isolated from analgesic fractions of methanolic extract of Cassia sieberiana DC., among which four new compounds and three new stereoisomers were identified. Eleven coumpounds were isolated from analgesic fractions of methanolic extract of Pericopsis laxiflora (Benth.) Meeuwen. This research work allowed us to deepen our knowledge about the chemical composition of Cassia sieberiana DC. and Pericopsis laxiflora (Benth.) Meeuwen and their potential analgesic activity.

This thesis investigated the phytochemistry and pharmacology of immunomodulatory medicinal plant species used traditionally by the Q’eqchi’ Maya Healers Association (QMHA) of Belize, and the Cree of Eeyou Istchee (CEI) of northern Quebec. Using quantitative ethnobotanical methodology, we identified 107 plant species belonging to 49 families used by Q’eqchi’ healers in the treatment of symptoms from 14 usage categories related to inflammation. Regression analysis revealed that the Piperaceae, Araceae, and Begoniaceae are preferentially selected by the Maya. Healer consensus for plant species was high, with 56 species (52%) being used by all the healers, and consensus for usage categories was also high, as informant consensus factor (FIC) values for each category were greater than 0.4. Fifty-two Belizean species were evaluated for their TNF-α inhibitory activity in an LPS-stimulated THP-1 monocyte model. Twenty-one species (40%) demonstrated significant TNF-α inhibition when assayed at 100 µg/mL, 8 of which had greater than 50% of the activity of the parthenolide positive control (10 µg/mL). Significant regressions were found between the anti-inflammatory activity and total healer frequency of use (Fuse) and the use reports for 3 usage categories, which indicated that ethnobotanical parameters can in part predict the activity of traditionally used species. Five sesquiterpene lactones were isolated from the leaves of Neurolaena lobata, one of the most active species tested, all of which demonstrated anti-inflammatory activity greater than that of parthenolide (IC50 = 4.79 µM), with IC50s ranging from 0.17-2.32 µM. Lobatin B was the most active isolate tested. Ethanolic and water extracts of 17 species used by Cree healers were evaluated for their immunomodulatory activity. In general, the average anti-inflammatory activity of ethanolic extracts was 1.8 times greater than that of water extracts, and the pro-inflammatory activity of water extracts was 3.7 times greater than ethanolic extracts. Picea mariana and Pinus banksiana were the most anti-inflammatory ethanolic and water extracts, while the water extract of Sarracenia purpurea was the most pro-inflammatory. Picea marina cones, the most anti-inflammatory Cree medicine, were subjected to bioassay guided isolation. This led to the isolation of the anti-inflammatory lignan (+)-lariciresinol-9’-p-coumarate, which had an IC50 of 28.4 µM. Together, these results validate the traditional knowledge shared by our Q’eqchi’ and Cree collaborators, and draw attention to the therapeutic potential of subtropical and boreal plants as culturally appropriate complements to modern medicine. - Cette thèse porte sur la phytochimie et la pharmacologie des espèces de plantes médicinales immunomodulatrices utilisées traditionnellement par le Q’eqchi’ Maya Healers Association (QMHA) du Belize, et les Cris d'Eeyou Istchee (CEI) du nord du Québec. En utilisant une méthodologie ethnobotanique quantitative, nous avons identifié 107 espèces végétales appartenant à 49 familles utilisées par les guérisseurs Q'eqchi’ dans le traitement de symptômes appartenant à 14 catégories d'utilisation liées à l'inflammation. Une analyse de régression a révélé que les familles Piperaceae, Araceae, et Begoniaceae sont préférentiellement choisis par les Mayas. Le consensus entre guérisseurs pour les espèces végétales était élevé, avec 56 espèces (52%) étant utilisés par tous les guérisseurs, et le consensus pour les catégories d'utilisation était également élevé, car les valeurs de facteur de consensus des informants (FIC) pour chaque catégorie étaient supérieurs à 0,4. Cinquante-deux espèces du Belize ont été évaluées pour leur activité inhibitrice de TNF-α dans un modèle de THP-1 monocytes stimulés par le LPS. Vingt-et-une espèces (40%) ont montré une inhibition significative de TNF-α lorsque dosés à 100 µg/mL, dont 8 d’entre elles ont démontrées plus de 50% de l'activité du contrôle positif parthénolide (10 µg/mL). Des régressions significatives ont été observées entre l'activité anti-inflammatoire et la fréquence d'utilisation de guérisseurs totale (Fuse) et les rapports d'utilisation pour 3 catégories d'utilisation, ce qui indique que les paramètres ethnobotaniques peuvent en partie prédire l'activité des espèces traditionnellement utilisées. Cinq lactones sesquiterpéniques ont été isolés à partir des feuilles de Neurolaena lobata, l'une des espèces les plus actives testées, qui a démontré une activité anti-inflammatoire supérieure à celle du parthénolide (CI50 = 4,79 µM), avec des CI50 allant de 0,17 à 2,32 µM. Lobatin B était l’isolât le plus actif testé. Des extraits éthanoliques et aqueux de 17 espèces utilisées par les guérisseurs Cris ont été évalués pour leur activité immunomodulatrice. En général, l'activité anti-inflammatoire moyenne des extraits éthanoliques était 1,8 fois supérieure à celle des extraits d'eau, et l'activité pro-inflammatoire des extraits d'eau était de 3,7 fois supérieure à celle des extraits éthanoliques. Picea mariana et Pinus banksiana étaient les extraits éthanoliques et aqueux avec le plus d’activité anti-inflammatoire, tandis que l'extrait aqueux de Sarracenia purpurea était le plus pro-inflammatoire. Le cône de Picea marina, le médicament traditionnelle Cris le plus anti-inflammatoire, a été soumis à une isolation guidée par essais biologiques. Cela a mené à l'isolement du lignane anti-inflammatoire (+)-lariciresinol-9'-p-coumarate, qui avait une CI50 de 28,4 µM. Ensemble, ces résultats valident les connaissances traditionnelles partagées par nos collaborateurs Q'eqchi' et Cris, et mettent en évidence le potentiel thérapeutique des plantes subtropicales et boréales comme des compléments à la médecine moderne qui sont culturellement appropriées.