A Amazônia peruana ocupa 62% do território do país. Ali existem 42 grupos etnolinguísticos, que apresentam características culturais, econômicas e políticas diferentes de outras populações do território nacional. Existe uma grande dívida histórica de reivindicação dos direitos destas populações, o que pressupõe elaborar formas de entender a dinâmica entre culturas diferentes, e projetando novas formas de relação que propiciem o encontro intercultural. Isso é importante para que a atenção à concepção, gravidez, parto e pós-parto se torne mais satisfatória e efetiva, e também para que sejam implementados serviços de saúde culturalmente adequados, com mais respeito aos direitos sexuais e reprodutivos no período gestacional. Objetivo: Conhecer as concepções sobre as necessidades específicas de saúde sexual e reprodutiva, com foco na saúde materna, no grupo étnico kukama kukamiria da comunidade de San Regis. Metodologia: Trata-se de um estudo qualitativo de base etnográfico, utilizando os instrumentos de entrevista aberta, observação participante e diário de campo. No total, foram realizadas 25 entrevistas individuais, com mulheres grávidas e puérperas, parteiras, médicos herbalistas, parceiros e servidores de saúde. A identidade dos participantes foi protegida com a utilização de nomes fictícios. Resultados: As mulheres grávidas costumam preferir os serviços das parteiras/ parteiros da comunidade de San Regis pelo vínculo emocional e afetivo entre as duas partes, que resulta numa atenção mais calorosa. As plantas e ervas medicinais são muito utilizadas para curar moléstias ou favorecer um melhor estado de saúde na gravidez, durante e depois do parto, além de serem usadas no cuidado do recém-nascido. Os serviços de saúde são menos procurados, por freqüentemente desrespeitos as tradições deste grupo kukama kukamiria e pelas técnicas inapropriadas que utilizam. Conclusão: As parteiras/parteiros são procuradas pela sua proximidade cultural e afetiva; nos serviços de saúde, freqüentemente a população se sente ameaçada pelo contato rude e procedimentos invasivos. / The Peruvian Amazon occupies 62% of the territory of the country. In such area there are 42 ethnolinguistic groups each presenting its own cultural, economic and political features, different from other groups within the national territory. A great historical debt exists in terms of the claims of these people, what calls for the construction of ways to understand the dynamics relations among the different cultures and for the proposal of new forms of relations allowing intercultural encounter. This is important so that the assistance given during conception, pregnancy, labor and the post-partum period may be more satisfactory and effective, and also for the implementation of culturally adequate health services which pay due respect to sexual and reproductive rights during the pregnant period. Objective: To know the representations of the specific sexual and reproductive health needs with a focus on maternal health, in the ethnic group Kukama Kukamiria, in the community called San Regis. Methodology: This is a qualitative ethnographic study, using the instruments of open interview, participating observation and field diaries. Altogether 25 individual interviews were made, with pregnant women and women in labor, birth attendants, herbal doctors, partners and health personnel. The identity of the participants has been protected by the use of fictitious names. Results: The pregnant women customarily prefer the services of male or female birth attendants of the San Regis community because of the emotional and affective links between the two sides which results in more humanized assistance. Medicinal plants and herbs are very used to cure ailments or produce a better state of health during pregnancy and during and after labor as well being used in the care of the new-born. The health services are less preterably sought after because of their frequent disrespect to the traditions of th-is kukama kukamiria group and because of the inappropriate techniques used. Conclusion: The male or female birth attendants are sought after due to their cultural and affective proximity; conversely, in the health services, people frequently feel threatened by the rude approach and invasive procedures.

O presente estudo analisou os efeitos da radiação gama na sobrevivência de fungos em plantas medicinais embaladas, adquiridas do comércio atacadista e varejista, em diferentes períodos (0 e 30 dias) após o tratamento por irradiação. Cinco tipos de plantas medicinais [Peumus boldus, Cameilia sinensis, Maytenus ilicifolia, Pauilinia cupana and Cássia angustifolia), foram coletadas de diferentes municípios do Estado de São Paulo e submetidas ao tratamento por irradiação, utilizando-se uma fonte 60Co (tipo Gammacell 220), com doses de 5,0 kGy e 10 kGy e taxa de dose de 3,0 kGy/h. Amostras não irradiadas (grupo controle) foram usadas na contagem de fungos e diluições seriadas de 10-1 a 10-6 das amostras foram semeadas em duplicata e plaqueadas usando o método de cultura em superfície, em ágar Dicloran Glicerol 18% (DG18) e contadas após cinco dias a 25°C. O grupo controle revelou a presença dos gêneros Aspergilius e Penicillium, os quais são conhecidos como fungos toxigênicos e poucas amostras do grupo controle estavam dentro dos limites seguros, estabelecidos pela Organização Mundial de Saúde (OMS, 1998) para plantas medicinais. Em resposta a resistência do tratamento por ionização, na dose de 5 kGy, foi obsen/ado que os gêneros Aspergilius, Piioma e Syncephalastrum foram radiorresistentes, após o processo (dia 0 e 30° dia). O tratamento por radiação gama foi efetivo na descontaminação de todas as amostras de plantas medicinais, após 30 dias, com a dose de 10 kGy e mantidas em condições de vedação. Não foram detectadas aflatoxinas nas amostras do grupo controle, ainda que estas amostras estivessem intensamente contaminadas com Aspergilius flavus. / This present study evaluated the effect of gamma radiation on the fungal survival in packed medicinal plants, purchased from wholesale and retail market, in different period (0 and 30 days) after the treatment. Five kind of medicinal plants (Peurnus boldus, Camellia sinensis, Maytenus ilicifolia, Pauilinia cupana and Cassia angustifolia), were collected from different cities of São Paulo State, and submitted to irradiation treatment using a 60Co source (type Gammacell 220) with doses of 5,0 kGy and 10 kGy and at dose rate of 3.0 kGy/h. Non-irradiated samples (control group) were used for fungal counts and serial dilutions from 10-1 to 10-6 of the samples were seeded in duplicates and plated using the surface culture method in Dichloran 18% Glycerol Agar (DG 18) and were counted after five days at 25°C. The control group revealed the presence of genera Aspergillus and Penicillium, which are known as toxigenic fungi and a few samples of control group were within the safety limits of World Health Organization (WHO, 1998) to medicinal plants. In response to resistance of ionizing treatment, in the dose of 5 kGy, it was obsen/ed that the genera Aspergillus, Phoma and Syncephalastrum were radio-resistant after the process (day 0 and 30° day). The treatment by gamma radiation was effective in decontamination of all irradiated samples of medicinal plants, after 30 days, with the dose of 10 kGy and kept of veiled conditions. It was not detected aflatoxins in samples of control group, even though these samples were heavily contaminated with Aspergillus flavus.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2014-09-09T12:33:09Z No. of bitstreams: 2 Dissertacao Natasha Queiroz Cardoso.pdf: 6356540 bytes, checksum: 9b1301eb1ac2488f6b8f0123c7dfeae7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-09T12:33:09Z (GMT). No. of bitstreams: 2 Dissertacao Natasha Queiroz Cardoso.pdf: 6356540 bytes, checksum: 9b1301eb1ac2488f6b8f0123c7dfeae7 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2013-02-28 / Lafoensia pacari A. St.-Hill (Lythraceae) popularly known as dedaleiro, didal, or mad-mangabeira pacari, is used by the Brazilian population as a febrifuge, tonic and healing. Studies have shown the antioxidant, anti-inflammatory, and antinoceptiva antiedematogenic extracts from the stem bark, ellagic acid being one of those responsible for the same. This study aimed to obtain dry extract standardized technology from the stem bark of L. pacari. The drug was tested for various quality control tests, according to the Brazilian Pharmacopoeia 5th edition, which ensured the characterization of plant drug and subsequently obtaining the liquid and dry extracts standardized. The extraction method was chosen slow percolation with 80% hydroalcoholic solution as a solvent and velocity of 7 drops per min .. The liquid extract standardized had a density of 0.986 g / mL solids content of 12.49% (w / w), pH 3.53 and an alcohol content of 44.80% (v / v). The content of ellagic acid found in liquid extract was 3.84% (m / m). The spray drying / atomization was performed by experimental design of univariate and then by planning a fractional 5-2 with 2 replicates. During the process the adjuvants were used maltodextrin and aerosil, demonstrating that the optimal conditions found maltodextrin provides greater protection and ellagic acid concentration in the extract. / Lafoensia pacari A. St.-Hill (Lythraceae) é conhecida popularmente como dedaleiro, didal, mangabeira-brava ou pacari, é utilizada pela população brasileira como febrífugo, cicatrizante e tônico. Estudos comprovaram as atividades antioxidante, antiinflamatória, antinoceptiva e antiedematogênica dos extratos provenientes das cascas do caule, sendo o ácido elágico um dos responsáveis pelas mesmas. O presente trabalho teve como objetivo a obtenção tecnológica de extrato seco padronizado a partir da casca do caule de L. pacari. A droga vegetal foi testada por diversos ensaios de controle de qualidade, de acordo com a Farmacopéia Brasileira 5ª edição, que garantiram a caracterização da droga vegetal e posteriormente a obtenção dos extratos líquidos e secos padronizados. O método de extração escolhido foi a percolação lenta com solução hidroalcóolica 80% como solvente e velocidade de 7 gotas por min.. O extrato líquido padronizado apresentou densidade de 0,986 g/mL, teor de sólidos de 12,49 % (m/m), pH 3,53 e teor alcoólico de 44,80% (v/v). O teor de ácido elágico encontrado no extrato líquido foi de 3,84%(m/m). A secagem por nebulização/atomização foi realizada por planejamento experimental de univariada e em seguida pelo planejamento fracionário 2 5-2 com replicatas. Durante o processo os adjuvantes utilizados foram a maltodextrina e o aerosil, demonstrando que nas condições ótimas encontradas a maltodextrina apresenta maior proteção e concentração de ácido elágico no extrato.

Les plantes médicinales constituent un réservoir important de substances naturelles pour la découverte de nouvelles molécules thérapeutiques. L’intérêt de ce travail est d'explorer le potentiel thérapeutique des plantes médicinales connues pour leurs vertus neuromodulatrices et potentiellement d’intérêt pour le traitement de maladies neurologiques, y compris l’épilepsie, en étudiant leur capacité à cibler l’activité des canaux calciques de type T qui jouent un rôle important dans l’hyperexcitabilité neuronale et la physiopathologie des épilepsies. Le premier objectif de ma thèse était d’étudier l’effet des extraits de plantes méditerranéennes ; Lavandula stoechas, Rosmarinus officinalis et Peganum harmala, ainsi que leurs principes actifs ; le linalol, l’acide rosmarinique et l’harmaline, respectivement, sur des courants calciques de type T en utilisant la technique patch-clamp en configuration cellule-entière. Les enregistrements électrophysiologiques à partir de cellules HEK-293 exprimant les canaux T montrent que la lavande, le romarin et l’harmal réduisent significativement les courants de type T sur la gamme de potentiel membranaire testée. Les produits naturels arrivent à déplacer l'état stable d’inactivation vers des potentiels de membrane plus négatifs et certains (Peganum harmala) accélèrent significativement la cinétique d'inactivation des canaux T. Le deuxième objectif était d’étudier l’effet anticonvulsivant et/ou antiépileptique de ces plantes et du TTA-A2 ; un bloqueur sélectif des canaux T, sur un modèle animal d’épilepsie. Nos résultats valident le PTZ et la 4-AP comme inducteurs de crises chez le poisson zèbre, ces deux modèles permettant le criblage pour des molécules anticonvulsivantes et/ou antiépileptiques. Nos résultats montrent que le romarin, la lavande ainsi que le TTA-A2 inhibent les crises pseudo-épileptiques chez ces deux modèles. Dans l’ensemble, ce projet suggère que les canaux T seraient impliqués dans les propriétés neuroprotectrices et anticonvulsivantes des plantes médicinales étudiées et valide le rôle des plantes médicinales comme source intéressante de produits thérapeutiques. / Medicinal plants represent an interesting reservoir of natural substances for the discovery of new therapeutic molecules. The interest of this work is to explore the therapeutic potential of medicinal plants, which are known for their neuromodulation effects, by studying their ability to target the activity of T-type calcium channels which play a major role in neuronal hyperexcitability and the pathophysiology of epilepsy and other neurological diseases.The first objective of my thesis was to study the effect of Mediterranean plant extracts; Lavandula stoechas, Rosmarinus officinalis and Peganum harmala and their active ingredients; linalool, rosmarinic acid and harmaline, respectively, on T-type calcium currents using the patch clamp technique in whole-cell configuration. Electrophysiological recordings from HEK-293 cells expressing T-type channels show that lavender, rosemary and Harmal significantly reduce T-type currents over the potential range tested. The natural products shifted steady-state inactivation towards more negative membrane potentials and some plants (Peganum harmala) significantly accelerate the inactivation kinetics of T-type channels. The second objective was to study the anticonvulsant / antiepileptic activity of these plants as well as TTA-A2, a selective T-type channel blocker, in an epilepsy model in zebrafish. Our results validate the PTZ and 4-AP as inducers of convulsions in zebrafish and both models could be used to screen for anticonvulsant and/or antiepileptic molecules. Our results show that rosemary, lavender and TTA-A2 inhibit seizures-like activity in these two models. Overall, this project suggests that T-type channels are involved in the neuroprotective and anticonvulsant properties of the studied medicinal plants and validates the role of medicinal plants as a valuable source of therapeutic products.

<p>У овој докторској дисертацији, комбуха је<br />култивисана на екстрактима ртањског чаја,<br />нане, коприве и мајчине душице заслађеним<br />са 7% сахарозе. Напици од комбухе добијени<br />на наведеним екстрактима су даље<br />коришћени као инокулуми за ферментацију<br />млека са 0,8; 1,6 и 2,8% млечне масти, на<br />температурама од 37, 40 и 43&deg;С.<br />Истраживање је обухватило праћење<br />антиоксидативне активности различитих<br />ферментисаних млечних производа<br />добијених помоћу комбухе, и то<br />утврђивањем способности везивања<br />слободних радикала, како веома реактивних<br />хидрокси-радикала, тако и мање реактивних,<br />стабилних 1,1-дифенил-2-пикрилхидразил<br />(DPPH) радикала. Урађена је<br />карактеризација млека, инокулума и<br />добијених производа утврђивањем физичко-<br />хемијских карактеристика, а у случају<br />производа и сензорном оценом. За млеко и<br />производе је измерен и садржај масних<br />киселина. Осим тога, одређени су и неки од<br />састојака производа за које се зна да имају<br />антиоксидативно деловање, при чему је<br />акценат стављен на витамин Це, као и<br />полинезасићене масне киселине.<br />Оптимизацијом температуре ферментације,<br />садржаја млечне масти полазног млека,<br />врсте инокулума комбухе, као и релевантних<br />састојака производа, утврђени су оптимални<br />услови за добијање најквалитетнијег<br />ферментисаног млечног производа од<br />комбухе са аспекта антиоксидативне<br />активности.</p> / <p>U ovoj doktorskoj disertaciji, kombuha je<br />kultivisana na ekstraktima rtanjskog čaja,<br />nane, koprive i majčine dušice zaslađenim<br />sa 7% saharoze. Napici od kombuhe dobijeni<br />na navedenim ekstraktima su dalje<br />korišćeni kao inokulumi za fermentaciju<br />mleka sa 0,8; 1,6 i 2,8% mlečne masti, na<br />temperaturama od 37, 40 i 43&deg;S.<br />Istraživanje je obuhvatilo praćenje<br />antioksidativne aktivnosti različitih<br />fermentisanih mlečnih proizvoda<br />dobijenih pomoću kombuhe, i to<br />utvrđivanjem sposobnosti vezivanja<br />slobodnih radikala, kako veoma reaktivnih<br />hidroksi-radikala, tako i manje reaktivnih,<br />stabilnih 1,1-difenil-2-pikrilhidrazil<br />(DPPH) radikala. Urađena je<br />karakterizacija mleka, inokuluma i<br />dobijenih proizvoda utvrđivanjem fizičko-<br />hemijskih karakteristika, a u slučaju<br />proizvoda i senzornom ocenom. Za mleko i<br />proizvode je izmeren i sadržaj masnih<br />kiselina. Osim toga, određeni su i neki od<br />sastojaka proizvoda za koje se zna da imaju<br />antioksidativno delovanje, pri čemu je<br />akcenat stavljen na vitamin Ce, kao i<br />polinezasićene masne kiseline.<br />Optimizacijom temperature fermentacije,<br />sadržaja mlečne masti polaznog mleka,<br />vrste inokuluma kombuhe, kao i relevantnih<br />sastojaka proizvoda, utvrđeni su optimalni<br />uslovi za dobijanje najkvalitetnijeg<br />fermentisanog mlečnog proizvoda od<br />kombuhe sa aspekta antioksidativne<br />aktivnosti.</p> / <p>In this PhD thesis, kombucha was cultivated on winter savory, peppermint, stinging nettle and wild thyme tea extracts, sweetened with 7% of sucrose. The kombucha beverages obtained on these extracts were used as inoculums for the fermentation of milk with 0.8; 1.6 and 2.8% milk fat, at temepratures of 37, 40 and 43&deg;С.<br />The investigation determined the antioxidant activity of different fermented milk products obtained by kombucha. The ability of free radicals (DPPH and hydroxyl) scavenging was established. The physicochemical characteristics of milk, inoculums and the obtained products were measured. The sensory analysis of the products was also performed. The content of fatty acids in milk and products was determined. The content of some of the product components with the antioxidant characteristics<br />(vitamin C and polyunsaturated fatty acids) was measured. Optimization of process temperature, milk fat content, type of kombucha inoculum, and relevant product components enabled the determination of optimum conditions for the obtaining of kombucha fermented milk products with the best quality, when the antioxidant activity is considered.</p>

Cheung, Ching Mei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 151-162). / Abstracts in English and Chinese. / ABSTRACT --- p.I / 論文摘要 --- p.IV / ACKNOWLEDGEMENT --- p.VI / TABLE OF CONTENTS --- p.VII / ABBREVIATIONS --- p.X / Chapter Chapter 1 --- p.1 / GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- DANSHEN --- p.1 / Chapter 1.1.1 --- LIPID-SOLUBLE COMPOUNDS EXTRACTED FROM DANSHEN --- p.2 / Chapter 1.1.1.1 --- TANSHINONE I --- p.2 / Chapter 1.1.1.2 --- TANSHINONE IIA --- p.3 / Chapter 1.1.1.3 --- CRYPTOTANSHINONE --- p.3 / Chapter 1.1.1.4 --- DIHYDROTANSHINONE --- p.4 / Chapter 1.1.2 --- WATER-SOLUBLE COMPOUNDS EXTRACTED FROM DANSHEN --- p.4 / Chapter 1.1.2.1 --- DANSHENSU --- p.4 / Chapter 1.1.2.2 --- SALVIANOLIC ACID B --- p.5 / Chapter 1.2 --- DRUG-DRUG INTERACTIONS --- p.5 / Chapter 1.2.1 --- PROBLEMS ASSOCIATED WITH HERBAL ADMINISTRATION --- p.5 / Chapter 1.2.2 --- HERB-DRUG INTERACTIONS --- p.7 / Chapter 1.2.2.1 --- ST. JOHŃةS WORT-DRUG INTERACTIONS --- p.8 / Chapter 1.2.2.2 --- WARFARIN-HERB INTERACTIONS --- p.9 / Chapter 1.2.2.3 --- DANSHEN-WARFARIN INTERACTIONS --- p.10 / Chapter 1.2.2.4 --- DANSHEN-DRUG INTERACTIONS --- p.11 / Chapter 1.3 --- CYTOCHROME P450 ENZYMES (CYP) --- p.12 / Chapter 1.3.1 --- CYTOCHROME P4502E1 --- p.13 / Chapter 1.4 --- AIMS OF STUDY --- p.17 / Chapter Chapter 2 --- p.21 / EFFECTS OF DANSHEN AND SOME IF ITS ACTIVE COMPONENTS ON CHLORZOXAZONE METABOLISM IN RAT AND HUMAN LIVER MICROSOMES IN VITRO --- p.21 / Chapter 2.1 --- INTRODUCTION --- p.21 / Chapter 2.2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.2.1 --- CHEMICALS AND REAGENTS --- p.23 / Chapter 2.2.2 --- PREPARATION OF AQUEOUS FRACTION OF DANSHEN --- p.23 / Chapter 2.2.3 --- PREPARATION OF ETHANOLIC FRACTION OF DANSHEN --- p.23 / Chapter 2.2.4 --- ANIMALS --- p.24 / Chapter 2.2.5 --- PREPARATION OF RAT LIVER MICROSOMES --- p.25 / Chapter 2.2.6 --- POOLED HUMAN LIVER MICROSOMES --- p.25 / Chapter 2.2.7 --- PROTEIN ASSAY --- p.25 / Chapter 2.2.8 --- MICROSOMAL INCUBATION --- p.26 / Chapter 2.2.8.1 --- RAT LIVER MICROSOMES --- p.26 / Chapter 2.2.8.2 --- HUMAN LIVER MICROSOMES --- p.26 / Chapter 2.2.9 --- INHIBITION KINETICS STUDIES --- p.27 / Chapter 2.2.9.1 --- RAT LIVER MICROSOMES --- p.27 / Chapter 2.2.9.2 --- HUMAN LIVER MICROSOMES --- p.27 / Chapter 2.2.10 --- HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS --- p.28 / Chapter 2.2.11 --- DATA ANALYSIS --- p.28 / Chapter 2.3 --- RESULTS --- p.31 / Chapter 2.3.1 --- EFFECT OF DANSHEN AND TANSHINONES ON RAT CYP2E1 ACTIVITY IN VITRO / Chapter 2.3.1.1 --- SUMMARY --- p.57 / Chapter 2.3.2 --- EFFECT OF DANSHEN AND TANSHINONES ON HUMAN CYP2E1 ACTIVITYIN VITRO --- p.58 / Chapter 2.3.2.1 --- SUMMARY --- p.84 / Chapter 2.4 --- DISCUSSION --- p.85 / Chapter Chapter 3 --- p.93 / EFFECTS OF DANSHEN ON CYTOCHROME P450 PROTEIN EXPRESSION AND METABOLISM OF MODEL CYP2E1 PROBE SUBSTRATE IN THE RAT IN VIVO --- p.93 / Chapter 3.1 --- INTRODUCTION --- p.93 / Chapter 3.2 --- MATERIALS AND METHODS --- p.97 / Chapter 3.2.1 --- CHEMICALS AND REAGENTS --- p.97 / Chapter 3.2.2 --- ANIMALS --- p.97 / Chapter 3.2.3 --- EFFECTS OF DANSHEN TREATMENTS ON PHARMACOKINETICS OF CHLORZOXAZONE IN RATS IN VIVO --- p.98 / Chapter 3.2.3.1 --- "ACUTE, 3-DAY AND 14-DAY TREATMENTS WITH WHOLE DANSHEN EXTRACT" --- p.98 / Chapter 3.2.3.2 --- PLASMA EXTRACTION --- p.99 / Chapter 3.2.3.3 --- HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS --- p.99 / Chapter 3.2.4 --- EFFECTS OF 3-DAY AND 14-DAY DANSHEN TREATMENTS ON CYP2E1 PROTEIN EXPRESSION --- p.101 / Chapter 3.2.4.1 --- PREPARATION OF RAT LIVER MICROSOMES FOR WESTERN BLOTTING --- p.101 / Chapter 3.2.4.2 --- PROTEIN ASSAY --- p.101 / Chapter 3.2.4.3 --- WESTERN BLOT --- p.102 / Chapter 3.2.5 --- DATA ANALYSIS --- p.103 / Chapter 3.3 --- RESULTS --- p.105 / Chapter 3.3.1 --- EFFECTS OF WHOLE DANSHEN EXTRACT ON RAT CYP2E1 ACTIVITIES IN VIVO --- p.105 / Chapter 3.3.1.1 --- EFFECTS OF ACUTE TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.105 / Chapter 3.3.1.2 --- EFFECTS OF 3-DAY TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.106 / Chapter 3.3.1.3 --- EFFECTS OF 14-DAY TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.107 / Chapter 3.3.2 --- EFFECTS OF WHOLE DANSHEN EXTRACT ON RAT CYP2E1 EXPRESSION .… --- p.137 / Chapter 3.3.3 --- SUMMARY --- p.140 / Chapter 3.4 --- DISCUSSION --- p.141 / CHAPTER 4 --- p.145 / GENERAL DISCUSSION --- p.145 / REFERENCES --- p.151

Os envenenamentos ofídicos constituem um problema relevante de saúde pública em diversas regiões do mundo, particularmente em países da zona tropical e neotropical. A fisiopatologia do acidente ofídico é constituída por uma série de eventos complexos tanto a nível local quanto sistêmico, e o soro antiofídico é o único tratamento utilizado. No entanto, os efeitos tóxicos locais induzidos durante o envenenamento por serpentes, principalmente do gênero Bothrops, não são eficientemente neutralizados pela soroterapia tradicional. Por esta razão, procuram-se alternativas complementares, como as plantas medicinais antiofídicas que são usadas por comunidades que não têm acesso a soroterapia. A flora brasileira possui uma ampla variedade de plantas medicinais com potencial antiofídico, as quais têm sido pouco estudadas cientificamente. Neste estudo foram realizados ensaios in vitro e in vivo de neutralização de peçonhas ofídicas com o extrato aquoso das entrecascas de Anacardium humile (EAAh), e, o isolamento e a caracterização fitoquímica de um inibidor de miotoxinas, o ácido gálico (AG). Para os ensaios de inibição, foram utilizadas soluções contendo peçonha bruta ou toxina isolada misturadas com diferentes quantidades de extrato vegetal que foram previamente incubadas por 30 min a 37°C. Também foi realizada administração do extrato após o envenenamento em diferentes intervalos de tempo para os testes de inibição da miotoxicidade. Observou-se que EAAh tem atividade inibitória sobre os efeitos tóxicos (letalidade, miotoxicidade, e hemorragia) e farmacológicos/enzimáticos (edema, atividade fosfolipásica e coagulante) induzidos pelas peçonhas de serpentes dos gêneros Bothrops, Crotalus, Lachesis e das toxinas isoladas. O extrato vegetal inibiu 100% a letalidade induzida pela peçonha de C. d. terrificus e sua principal neurotoxina, a crotoxina. O EAAh foi submetido a fracionamento cromatográfico analítico, e em condições polares foi possível identificar e isolar o ácido gálico, o qual demonstrou tempo de retenção e espectros de ressonância magnética nucleares similares ao padrão comercial e a dados de literatura deste mesmo composto, respectivamente. O ácido gálico isolado foi capaz de inibir a atividade miotóxica induzida pela peçonha bruta de B. jararacussu e sua principal miotoxina, a bothropstoxina-I, uma PLA2-símile Lys49. A análise dos espectros de dicroísmo circular e os estudos de interação por modelagem molecular sugerem que o ácido gálico forma um complexo com a BthTX-I de B. jararacussu em seu sítio ativo, inibindo sua atividade tóxica. A ligação do ácido gálico com as miotoxinas não modificou nem a forma e nem a intensidade dos espectros de dicroísmo circular, não induzindo alterações significativas na porcentagem dos diversos domínios que constituem a estrutura secundária destas proteínas. O ácido gálico assim como outros taninos, tem revelado-se um bom inibidor das ações tóxicas de peçonhas de serpentes e está relacionado com a ação inibitória do extrato de Anacardium humile. / Ophidian envenomations are a significant problem of public health in several regions of the world, particularly in tropical and neotropical countries. The pathophysiology of snakebite accidents is constituted by a complex series of events both locally and systemically, and the antivenom serum is the only treatment used. However, local toxic effects induced during envenomation by snakes, especially from the genus Bothrops, are not effectively neutralized by the traditional serum therapy. For this reason, additional alternatives are made necessary, such as the use of medicinal plants that are used by communities with no access to serum therapy. The Brazilian flora possesses a wide variety of medicinal plants with antiophidian potential, which have been little-studied scientifically. In the present study, we performed in vitro and in vivo neutralization of snake venoms with the aqueous extract of inner bark of Anacardium humile (EAAh), and the isolation and phytochemical characterization of an inhibitor of myotoxins, the gallic acid (GA). For the inhibition assays, we used solutions containing crude venom or isolated toxin mixed with different amounts of plant extracts that were previously incubated for 30 min at 37°C. Administration of the extract after envenomation was also performed at different time intervals for myotoxicity inhibition assays. It was observed that EAAh has inhibitory activity against the toxic (lethality, myotoxicity and hemorrhage) and pharmacological/enzymatic effects (edema-inducing, coagulant and phospholipase activities) induced by snake venoms of the genera Bothrops, Crotalus, Lachesis and isolated toxins. The plant extract inhibited 100% of the lethality induced by C. d. terrificus venom and its major neurotoxin, crotoxin. The EAAh was subjected to analytical chromatographic separation, and in polar conditions, it was possible to identify and isolate the gallic acid, which showed retention time and nuclear magnetic resonance spectra similar to the commercial standard and to literature data of this same compound, respectively. Gallic acid alone was able to inhibit the myotoxic activity induced by crude venom of B. jararacussu and its main myotoxin, BthTX-I, a Lys49 PLA2-like enzyme. The analysis of circular dichroism spectra and interaction studies by molecular modeling suggest that gallic acid forms a complex with BthTX-I in its active site, which inhibits its toxic activity. The binding of gallic acid to myotoxins did not change neither the form nor the intensity of circular dichroism spectra, not inducing significant changes in the percentage of the various domains that form the secondary structure of these proteins. The gallic acid and other tannins have been showed to be good inhibitors of the toxic effects of snake venoms, and our study showed that this acid is related to the inhibitory action of the Anacardium humile extract.

Orientador: Luis Vitor Silva do Sacramento / Banca: João Domingos Rodrigues / Banca: Celso Dornellas Fernandes / Resumo: Cymbopogon citratus (DC.) Stapf é uma gramínea perene, de grande importância para a indústria farmacêutica e alimentícia, fornecedora de óleo essencial. Um problema limitante para a produção comercial é a ferrugem, causada pelo patógeno Puccinia nakanishikii Dietel. O trabalho objetivou estudar a interação patógeno-hospedeiro e availar princípios ativos naturais no controle da doença. Para os estudos anatômicos foram elaborados cortes, objetivando analisar as estruturas lesionadas e o desenvolvimento do patógeno. Foram avaliadas as trocas gasosas nas diferentes severidades da doença. Realizaram-se testes in vitro, com diferentes agentes de controle sobre a germinação de esporos do patógeno, sendo estes: óleos essenciais de eucalipto, palma-rosa, cravo-da-índia, menta, limão, citronela e mil-folhas; extrato pirolenhoso de eucalipto e mentol cristalizado. A partir destes testes foram escolhidos quatro agentes para os testes em campo, óleo de citronela e de eucalipto, extrato pirolenhoso e mentol. A área foi preparada a partir de mudas, sendo manejadas até os seis meses. Quando todas as plantas apresentavam sintomas, iniciaram-se os tratamentos com aplicações semanais. Foi avaliada ainda a doença após um corte. Os sintomas iniciais manifestam-se como manchas amareladas evoluindo para a formação de pústulas bronzeadas alongadas. Quanto à avaliação anatômica, após a infecção houve o desenvolvimento das estruturas fúngicas, prosseguindo com o rompimento da cutícula, possibilitando a observação das estruturas do patógeno de forma clara sobre as células da epiderme. Nas regiões lignificadas dos feixes vasculares não há desenvolvimento dessas estruturas. Com o aumento da severidade da doença observou-se a redução da assimilação de gás carbônico. A concentração interna de gás carbônico foi maior em severidades mais altas. Tal fato relaciona-se... (Resumo completo clicar acesso eletrônico abaixo) / Abstract: Cymbopogon citratus (DC) Stapf is a perennial grass, that has a large importance to the pharmaceutical and food industry, supplier of essential oil. One limiting problem to the commercial production is the rust caused by pathogen Puccinia nakanishikii Dietel. This work aimed to investigate the pathogen-host interactions and contribute to the researches with alternative methods of disease control. For anatomical studies were prepared anatomical sections, with the objective to analyze the structures injured and the development of the pathogen with different corants. On cultivated plants were evaluated gas exchange in different severity levels. In vitro tests were performed with different control agents, to the germination of pathogen spores, which are: essential oil of eucalyptus, palmarosa, clove, peppermint, lemon, citronella and yarrow; pyroligneous extract of eucalyptus and crystallized menthol. From these tests four products were chosen for the tests in a camp experiment, citronella oil, eucalyptus oil, pyroligneous extract and menthol. The area was prepared from seedlings, which were managed by six months age. When all plants had symptoms the treatments begin, with weekly applications. One avaliation happened after the cut of the lemongrass. The initial symptoms manifest as yellow spots progressing to formation of elongated pustules. These symptoms beginning with the development of fungal structures, after occurred the disruption of the cuticle, so the structures of the pathogen may be clearly observed on epidermis parenchyma cells of the leaf abaxial surface, however, in regions of vascular bundles, no development of such structures, these regions that have lignified structures. With the increase of the disease severity was a significant reduction in the assimilation of carbonic gas. The internal concentration of carbon dioxide was major... (Complete abstract click electronic access below) / Mestre

Thesis (M.Sc. (Biochemistry)) -- University of Limpopo, 2013 / Diabetes mellitus is one of the fast growing chronic metabolic disorders throughout the world. It has become a life threatening disease and health burden. So far it can only be managed with commercial therapeutic agents, proper diet and exercise. People particularly from developing countries use medicinal plants to treat this condition. According to WHO, about 80% of the population in developing countries are dependable on medicinal plants. This prompted many researchers to explore the effectiveness and safety of these plants. In the current study ten medicinal plants were randomly chosen, screened for antidiabetic activity by testing their ability to inhibit α-amylase and α-glucosidase enzymes. The plants were tested using in vitro assays. The finely powdered leaves of each plant were extracted with hexane, chloroform, acetone and ethyl acetate. Phytoconstituents of each plant extracts were analyzed using both qualitative and quantitative methods. All plant extracts tested positive for phenols, flavonoids and all negative for starch. Their compounds were better separated in the TEA mobile system on the TLC plates. All plant extracts had more of total phenolics ranging between 0.1-400 GAE/mg than total flavonoids and condensed tannins. Antioxidant activity of the plant extracts was tested quantitatively at various concentrations using DPPH. Most plant extracts were able to scavenge the radicals produced by DPPH at highest concentration of 2.5 mg/mℓ. Not all plant extracts with the highest number of total phenolics had the highest antioxidant activity. For antidiabetic in vitro assays, plant extracts inhibited various percentages of both α-amylase and α-glucosidase activity at concentrations ranging between 0.019- 2.5 mg/mℓ. The best overall activity against both enzymes was observed in acetone and ethyl acetate plant extracts. Cassia abbreviata and Helinus integrifolius were even more active than acarbose which was used as positive control. These plant extracts inhibited both the enzymes in a dose dependent and non-competitive manner. Seeing that both extracts of C. abbreviata and H. integrifolius were consistent when inhibiting both enzymes, they were further evaluated for their effect on glucose uptake by the C2C12 muscle and H-II-4-E liver cells. All the plant extracts tested were able to increase glucose uptake in the muscle cells. However optimal increase was seen in the liver cells when treated with 250 µg/mℓ of acetone and ethyl acetate extracts of C. abbreviata. The cytotoxicity effects of both acetone and ethyl acetate of C. abbreviata and H. integrifolius was tested using the xCelligence system on RAW 264.7 cells. Different cell indexes were obtained after treating the cells with different concentrations (0.05,0.1 and 0.25 mg/mℓ) of each plant extracts respectively. The system was run for three days but the toxic effects of plant extracts were analyzed for the first ten hours. The results obtained shows that cell index decreased as the concentration of the plant extracts was increased. All the plant extracts were less toxic as compared to positive control, Actinomycin D. The leaves of H. integrifolius were further exhaustively extracted with hexane, dichloromethane, acetone, ethyl acetate and methanol respectively. Since the DCM extracts yielded the highest mass in quantity, it was further used for isolation of active compounds. Column chromatography and bioassay guided fraction led to isolation of a mixture of triterpenes identified as α and β-amyrin. The structure was elucidated using nuclear magnetic resonance technique. The inhibitory capability of the isolated compound against α-amylase enzyme was less than the crude extract which inhibited more than 50% of the activity at a concentration of 1 mg/mℓ.Based on the enzymes assays and cell culture work it can be concluded that C. abbreviata and H. integrifolius species are the best inhibitors of carbohydrate digesting enzymes, and therefore be used to manage postprandial hyperglycemia in the people with type 2 diabetes. However more work still need to be conducted for further isolation of more active compounds.

Thesis (M.Sc. (Biochemistry )) --University of Limpopo, 2007 / Refer to document / The Cannon Collins Trust Fund and the National Research Foundation