Doctorat en Sciences / info:eu-repo/semantics/nonPublished

L’industrie parapharmaceutique de même que l’industrie cosmétique recherche des alternatives naturelles aux conservateurs synthétiques. Cet intérêt est lié à l’exigence du consommateur et à la volonté de développer des produits innovants éco-conçus. Compte tenu de leurs activités antioxydantes et antimicrobiennes, les huiles essentielles constituent des options intéressantes dont les coûts et impacts organoleptiques doivent cependant être considérés. Dans le cadre de cette thèse, les activités antioxydante et antimicrobienne de combinaisons huile essentielle-hydrolat et huile essentielle-huile essentielle de Lippia alba, Rosmarinus officinalis et Thymus vulgaris ont été évaluées afin d’objectiver leur potentiel de conservateur pour des produits phytothérapeutiques. Initialement, l’impact d’une méthode de distillation utilisant le macérât aqueux de la matière végétale comme source de vapeur a été évalué sur les propriétés physico-chimiques des hydrolats et huiles essentielles de Thymus vulgaris et Rosmarinus officinalis cultivées dans le sud de Bogotá en Colombie. Puis, les distillats et hydrolats ayant présenté une activité biologique significative ainsi que l’huile essentielle de Lippia alba ont été combinés deux à deux. Les activités antiradicalaire et microbicide ont été évaluées respectivement par ABTS et par les méthodes de microdilution et de diffusion en agar. Des résultats biologiques significatifs ont été obtenus pour les combinaisons huile essentielle-huile essentielle tout spécialement dans le cas de la combinaison des huiles essentielles de T. vulgaris et de L. alba avec une diminution de la CI50 de 2,9 (huile essentielle de Thym seule) à 1,4 µL/L ainsi que dans le cas spécifique de la combinaison hydrolat-huile essentielle de Thymus vulgaris avec une CI50 de 2,1 µL/L. De même, cette dernière combinaison a présenté un effet de synergie en diminuant la Concentration Minimale Bactéricide de l’huile essentielle de Thym de 0,4 à 0,1 µL/mL. Les différents résultats sont discutés ainsi que leurs impacts d’un point de vue industriel et thérapeutique.

Previous research into complementary and alternative medicine has failed to accord each form of alternative medical intervention individual significance. This research considers medical herbalism in Britain and investigates the re-presentation of its knowledge within a scientific framework as a strategy in a process of professionalisation. Data were gathered from herbalists' own statements that provided the answers to how? and why? this occurred. Whilst it is suggested that much science is heavily influenced by its social and cultural enviromnent, the tenacious portrayal of biomedicine as science is taken as accepted orthodoxy. Dolby's model, whereby unorthodox science assumes the features of orthodox science to become accepted as science, is forwarded as an explanation of how herbal medicine has been re-presented as phytotherapy and therefore 'scientific'. The influences of the sociocultural enviromnent and the sociopolitical enviromnent on herbalism's recognition and acceptance by both the state and conventional medicine are suggested as explanations of why phytotherapy has been promoted by some herbalists. It is noted that such transformative measures have not radically affected the professional practice of medical herbalists, nor are they universally welcomed. The anomaly between institutional education of herbalism in terms of phytotherapy and the continuing practice of herbalism as a 'tradition' is noted. The relative identities of practitioners - with a cultural identity - and herbal institutions - with a social identity - is suggested as the explanation for the discontinuity between institutional knowledge and actual practice. It is also argued that medical herbalists have an element of altruism in their practice that is noteworthy beyond an assumed professional service orientation. Herbalists' differences of view regarding the acceptability of promoting phytotherapy as a route to recognition and acceptance appear to be subordinated by fears and anxieties about possible future govermnent legislation and EU harmonisation regulations.

Les préparations de Viscum album (VA), connu sous le nom vernaculaire de gui européen, sont fréquemment utilisées en support des traitements anticancéreux, principalement pour améliorer la qualité de vie des malades et réduire la croissance des tumeurs. Elles sont connues pour exercer des effets anti-tumoraux. Il existe de plus en plus de données scientifiques faisant état de liens étroits entre cancer et inflammation. Étant donné que la prostaglandine E2 (PGE2) induite par la cyclo-oxygénase 2 (COX-2) joue un rôle clef dans l’inflammation, j’ai exploré la régulation du système COX-2-PGE2 par VA et ses mécanismes sous-jacents. J’ai montré que VA exerce ses effets anti-inflammatoires en inhibant sélectivement l’expression de COX-2 et en diminuant la production de PGE2 qui en découle, par le biais d’une déstabilisation de l’ARNm de COX-2. En plus de leurs propriétés cytotoxiques, il a été montré que les préparations de VA ont également des effets immunostimulants. Les différentes préparations de VA sont hautement hétérogènes du fait de leurs compositions biochimiques qui varient selon la récolte, l’espèce de l’arbre hôte et les méthodes de préparation qui peuvent influer sur leur efficacité clinique. De ce fait, j’ai réalisé une étude comparative sur cinq préparations de VA dans le but d’analyser leurs capacités de maturation et d’activation des cellules dendritiques (DC) qui peuvent à leur tour présenter une réponse immunitaire anti-tumorale. Les résultats ont montré que parmi les cinq préparations,VA Qu Spez induit de manière significative l’activation des DC et la sécrétion de cytokines pro-inflammatoires telle que l’IL-6, l’IL-8 et le TNF-α qui induisent la production d’IFN-γ,orientant de ce fait la réponse immunitaire vers une réponse Th1. L’orchestration de la11fonction des cellules myélomonocytiques est un élément central à l’interface entre inflammation et cancer. Il constitue un paradigme expliquant la plasticité et la fonction des macrophages. Mon étude met en évidence l’influence de VA Qu Spez sur la polarisation des macrophages qui passent d’un état alternatif (M2) à un état dit classique (ou M1). Les macrophages M2 sont connus pour polariser les réponses immunitaires Th2, pour participer à l’élimination des parasites, pour diminuer l’inflammation, pour promouvoir le remodelage tissulaire et la progression des tumeurs et pour avoir des fonctions immunorégulatrices. Les macrophages M1 sont impliqués dans la réponse Th1, favorisent la résistance aux pathogènes intracellulaires et aux tumeurs et promeuvent des réactions de désagrégation tissulaires. L’ensemble de ces résultats permet de comprendre les propriétés anti-inflammatoires et immunostimulantes des préparations de VA. Des recherches complémentaires permettront d’améliorer les stratégies d’utilisation thérapeutique de VA et son utilisation dans les soins de support aux traitements anticancéreux. / Viscum album (VA) preparations, commonly known as European mistletoe, are frequentlyused as complementary therapy in cancer, mainly to improve quality of life of the patients andto reduce the tumor growth. They are known to exert anti-tumoral effects. There is increasing evidence of the convoluted connection of cancer and inflammation. As cyclooxygenase-2(COX-2)-induced prostaglandin E2 (PGE2) plays a key role in the inflammation, I explored the regulation of COX-2-PGE2 axis by VA and underlying mechanisms. I found that VA exerts anti-inflammatory effects by selectively inhibiting COX-2 expression and ensuing PGE2 production. Inhibition of COX-2 expression implicates COX-2 mRNA destabilisation. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. Each VA preparations are highly heterogeneous because oftheir chemical composition which varies depending on the time of harvest, species of host treeand manufacturing methods, together which might influence clinical efficacy of VA.Therefore I performed a comparative study involving five different preparations of VA concerning maturation and activation of dendritic cells (DCs) which in turn may manifestanti-tumoral immune response. Results showed that among all five preparations, VA Qu Spez significantly induces DC activation, secretion of pro-inflammatory cytokines such as IL-6, Il-8 and TNF-α, enhancing IFN-γ production hence promoting Th1 immune response. The orchestration of myelomonocytic cell function is a key element that links inflammation and cancer and provides a paradigm for macrophage plasticity and function. My study reveals the effect of VA Qu Spez in switching the M2 macrophages which are known to participate inpolarizing Th2 responses, help with parasite clearance, dampen inflammation, promote tissue remodelling and tumor progression and have immunoregulatory functions, towards classicallyactivated M1 macrophages which are part of a polarized Th1 response and mediate resistance13to intracellular pathogens and tumors and elicit tissue-disruptive reactions. These results together should assist in understanding the anti-inflammatory and immunostimulatory properties of VA preparations and further research is warranted to improve the therapeutic strategies of use of VA and their role as complimentary therapy in cancer.

Magister Scientiae - MSc / This study aimed to evaluate the antimicrobial efficacy of medicinal hemp plant extracts to determine the antibacterial effects of indigenous Sansevieria species and exotic Cannabis sativa phytotherapy varieties. This study also assessed whether aqueous o / South Africa

Magister Scientiae - MSc / In South Africa, the crude aqueous extract from Hypoxis hemerocallidea is used by AIDS patients to treat opportunistic infections, such as tuberculosis. The rapid emergence of multidrug-resistant tuberculosis, and extreme drug resistant tuberculosis, in recent years, is a major threat to human health. The treatment of TB, nosocomial bacterial infections, and fungal infections is now a clinical challenge, especially in the immuno-compromised individual. There is a dire need for novel antibiotic alternatives with phytotherapies and plant-derived compounds as potentially promising alternatives. The main objective of this study was to investigate the antimycobacterial activity of Hypoxis hemerocallidea, a South African medicinal plant, using Mycobacterium smegmatis. / South Africa

Philosophiae Doctor - PhD / The reproductive health of individuals is severely compromised by HIV infection, with candidiasis being the most prevalent oral complication in patients. Although not usually associated with severe morbidity, oropharyngeal candidiasis can be clinically significant, as it can interfere with the administration of medications and adequate nutritional intake, and may spread to the esophagus. Azole antifungal agents are commonly prescribed for the treatment and prophylaxis of candidal infections. However, the emergence of drug resistant strains and dose limiting toxic effects have complicated the treatment of candidiasis. Consequently, safe and effective and affordable medicine is required to combat this fungus. Commercial garlic (Allium sativum) has been used time since immemorial as a natural antibiotic, however very little is known about the antifungal properties of two indigenous South African species of garlic, namely Tulbaghia alliacea and Tulbaghia violacea, that are used as folk medicines for a variety of infections. This study compares the in vitro anti-candidal activity of Tulbaghia alliacea, Tulbaghia violacea and Allium sativum extracts. It was found that the greatest concentrations of inhibitory components were extracted by chloroform or water. The IC50 concentrations of Tulbaghia alliacea were between 0.007 - 0.038% (w/v). Assays using S. cerevisiae revealed that the T. alliacea extract was fungicidal, with a killing half-life of approximately 2 hours. This inhibitory effect of the T. alliacea extracts was observed via TLC, and may be due to an active compound called Marasmicin, that was identified using NMR. This investigation confirms that extracts of T.alliacea exhibit anti-infective activity against candida species in vitro. / South Africa

Submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homeopathy, Durban University of Technology, Durban, South Africa, 2016. / INTRODUCTION Dysmenorrhoea is defined as difficult menstrual flow or painful menstruation. Dysmenorrhoea is the most common gynaecological complaint in younger women who present themselves to clinicians. Primary dysmenorrhoea is defined as painful menstrual cramps without any evident pathology present. It refers to any degree of perceived cramping pain experienced during menstruation. Around 50% of menstruating females suffer from primary dysmenorrhoea. Prevalence decreases with age, with prevalence being highest in the 20 to 24 year old age group. This trial intended to evaluate the effectiveness of a phytotherapeutic complex in the treatment of primary dysmenorrhoea compared to homoeopathic similimum in a 30 cH plussed potency. This study aimed to provide the safe and effective alternative therapy for primary dysmenorrhoea, especially for the population that is contradicted to use the readily available forms of treatments. TRIAL DESIGN This double-blind randomised parallel clinical trial, aimed to determine the effectiveness of a phytotherapeutic complex consisting of Angelica sinensis1:10, Dioscorea villosa1:10, Matricaria chamomilla 1:10, Viburnum opulus 1:10, and Zingiber officinalis 1:10 in the treatment of primary dysmenorrhea, compared to homoeopathic similimum in a 30cH plussed potency. METHODOLOGY A sample group of 26 participants were voluntarily selected for the study on the basis of an inclusion and exclusion criteria. These participants were then randomly divided into two groups, 17 in the group receiving the phytotherapeutic complex, 8 in the control group receiving the similimum and 1 drop-out. Each participant had to attend a total of four consultations with the researcher over a three month period, at the Durban University of Technology (DUT) Homoeopathic Day Clinic. At each consultation the participant completed the Moos Menstrual Distress Questionnaire (MDQ) (Appendix B) as well as the Pain Rating Scale (PRS) (Appendix C). Intra-group analysis was performed using the non-parametric test for analysis of variance: Friedman’s test. Inter-group analysis was conducted using the Mann- Whitney U test for two independent samples. RESULTS Results from the intra-group analysis showed that in both groups most measured parameters relating to experience during the previous menstrual flow showed statistically significant reductions in intensity. This is to say that both the group receiving phytotherapy and the group receiving similimum experienced reductions in their symptoms as measured by both the MDQ and the PRS. Results from the inter-group analysis showed that there is no significant difference between the phytotherapy and similimum group in all symptoms except the water retention category, with regard to symptom perception during the last menstrual flow of the trial. CONCLUSION The conclusion reached in this study was that both the phytotherapeutic complex treatment and the homoeopathic similimum treatment were effective at reducing the clinical features of primary dysmenorrhea, but there was no significant difference between the phytotherapy and similimum group in all except the water retention category during the last menstrual period as measured by the MDQ Further, there was no statistically significant difference between groups treated with phytotherapy compared to similimum as measured by the PRS. / M

Submitted by Gabriela Lopes (gmachadolopesufpel@gmail.com) on 2018-11-20T12:22:41Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao PNPMF_EduardoRSM.pdf: 3987157 bytes, checksum: 2b0502c26f9d26a493b6a69304ae9cf2 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2018-11-23T18:41:40Z (GMT) No. of bitstreams: 2 Dissertacao PNPMF_EduardoRSM.pdf: 3987157 bytes, checksum: 2b0502c26f9d26a493b6a69304ae9cf2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-11-23T18:41:40Z (GMT). No. of bitstreams: 2 Dissertacao PNPMF_EduardoRSM.pdf: 3987157 bytes, checksum: 2b0502c26f9d26a493b6a69304ae9cf2 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-07-25 / Sob a orientação da Política Nacional de Plantas Medicinais e Medicamentos Fitoterápicos (PNPMF), marco legal para a utilização das plantas medicinais no Sistema Único de Saúde, a academia vem desenvolvendo pesquisas sobre as plantas medicinais para dar suporte e base científica às diretrizes da PNPMF. No geral a produção acadêmica neste segmento acompanha movimentos e tendências de interesse da sociedade ao longo dos 12 anos da PNPMF. Neste período, diversas iniciativas vêm ocorrendo no sentido de efetivar a PNPMF nos municípios. O estudo destas experiências e iniciativas pode amparar e corrigir os rumos dos atores sociais que agem movidos pelas diretrizes desta política. Devido à complexidade do processo, não há fórmula que possa definir o rumo e as ações, sendo estas específicas de cada município de acordo com sua realidade. Há uma lacuna na produção científica em estudos de caso sobre os métodos e estratégias utilizados pelos atores sociais nestas experiências e no dimensionamento da produção de plantas para atender à população do município. Neste contexto, este estudo de caso acompanhou as ações e metodologias empregadas pelos atores sociais para inserção de plantas medicinais no SUS do município de Turuçu-RS, com a participação dos agricultores familiares na cadeia produtiva. Os resultados obtidos permitem concluir que a cadeia produtiva curta e descentralizada, e o perfil epidemiológico como método para seleção de plantas medicinais foram adequados para estruturar e dimensionar a produção de drogas vegetais para o município de Turuçu. / Under the guidance of the National Policy of Medicinal Plants and Phytotherapeutic Medicines (PNPMF), legal framework for the use of medicinal plants in the Unified Health System, the academy has been developing research on medicinal plants to provide support and scientific basis to PNPMF guidelines. In general, the academic production in this segment accompanies movements and tendencies of interest of society throughout the 12 years of PNPMF. During this period, several initiatives have been taking place in order to implement PNPMF in the municipalities. The study of these experiences and initiatives can support and correct the course of the social actors who act by the guidelines of this policy. Due to the complexity of the process, there is no formula that can define the direction and the actions, being these specific of each municipality according to its reality. There is a gap in scientific production in case studies on the methods and strategies used by social actors in these experiments and in the design of plant production to meet the population of the municipality. In this context, this case study followed the actions and methodologies used by social actors to insert medicinal plants into SUS in the municipality of Turuçu-RS, with the participation of family farmers in the production chain. The results obtained allow us to conclude that the short and decentralized production chain and the epidemiological profile as a method for selecting medicinal plants were adequate to structure and size the production of vegetal drugs for the municipality of Turuçu.

[pt] A presente tese inserida no campo da Geografia da saúde, contextualiza o uso de plantas medicinais e apresenta a sua retomada nos sistemas oficiais de saúde dos países membros da OMS, principalmente no território brasileiro após o nascimento do SUS e da criação da Política Nacional de Plantas Medicinais e Fitoterápicos (PNPMF). Considerando a distribuição desigual da medicina moderna nos territórios, o uso de plantas permaneceu sendo alternativa de cuidado para pessoas que têm acesso restrito à assistência médica e aos medicamentos industrializados e também por populações que possuem forte vínculo com os territórios em que vivem. A tese teve como principal objetivo compreender os obstáculos do desenvolvimento da PNPMF no Brasil. Além de compreender se houve a valorização dos saberes tradicionais e da biodiversidade brasileira, como recomenda a PNPMF , de entender se a fitoterapia praticada no SUS tem impacto nas formas de cuidado com a saúde e de verificar a destribuição geográfica das empresas que produzem os fitoterápicos no Brasil. A pesquisa foi dividida em quatro etapas. A primeira etapa, em que colhemos os dados primários, foi realizada através de entrevistas semi- estruturadas em profundidade com atores importantes na criação e no desenvolvimento da PNPF A segunda etapa foi realizada através da analise das atas das reuniões do Comitê Gestor da Política Nacional de Plantas Medicinais e Fitoterápicos, a terceira etapa foi feita através da analise da lista de 1483 registros de fitoterápicos disponíveis no site da Anvisa e a quarta fonte de informações foi uma pesquisa em base de dados com 14 espécies nativas do Brasil, retiradas de cartilhas populares afim de verificar o potencial fitogeográfico e tecnociêntífico dessas espécies. Através de uma triangulação dos dados, em que a Anvisa e a literatura especializada representam o conhecimento técnico- científico, as cartilhas populares representam o conhecimento tradicional e as espécies nativas representam o território, as relações, saberes e formas de cuidado, concluímos que após 15 anos da criação da PNPMF não houve valorização da biodiversidade e do conhecimento tradicional, pois a maioria dos fitoterápicos comercializados no Brasil são elaborados a partir de espécies exóticas ou adaptadas. Não houve fomento á criação ou permanência de empresas brasileiras, pois as exigências da Anvisa não as favorece, é limitado o número de pesquisas científicas com espécies nativas e não há verba suficiente para o desenvolvimento desses programas nas unidades de atenção primária da saúde, pois não existe uma lei que viabilize investimentos para isso. Em relação á transformação e oferta de outras formas de cuidado, autocuidado e autoatenção não acontece, pois os programas utilizam mais fitoterápicos industrializados seguido os moldes da medicina moderna, prescritiva e focada nos sintomas, estando o conhecimento das espécies e do uso, portanto da ligação com esta prática de cuidado com a autonomia e autoatenção vinculado com a falta de acesso aos serviços da medicina. / [en] His tesis, inserted in the field of health geography contextualizes the use of medicinal plants and presents its resumption in the oficial health systems of countries members of the WHO and mainly in the Brazilian territory after the birth of the SUS and the creation of the National Policy on Medicinal Plants and Herbal Medicines. Considering the unequal distribution of modern medicine in the territories, the use of plants remained a care alternative for people who have restricted access to medical care and industrialized medicines, usually residing in peripheral and economically vulnerable areas. In order to understand the obstacles to the development of the PNPMF in Brazil, the appreciation of appreciation of traditional knowledge, the Brazilian biodiversity that has a significant number of medicinal plants, and therefore with potential for the development of the national herbal medicine industry and also to understand how to inclusion of this pratice in primary health care has the potential to contribute to new forms of care and self- care. The research was divided into four stages. The first stage, in which we collected the primary data, was carried out through in- depth semi- structured interviews with importante actors in the creation and development of the PNPMF.The second stage was carried out through the analysis of the meetings of the Management Committee of the National Policy on Medicinal Plants and Herbal Medicines, the third stage was carried out through the analysis of the list of 1483 records of herbal medicines available on the ANVISA website, through which the number of native species used in the manufacture of medicines, the geographic distribution of the companies that manufacture them in Brazil, and the fourth source of information was a database search with 14 native species from Brazil, taken from related popular booklets to verify the phytogeographic and technoscientific potential of these species. Through a triangulation of data, in which Anvisa and specialized literature represent technical-scientific knowledge, popular booklets represent traditional knowledge and native species represent the territory, relationships, knowledge and forms of care, we conclude that after 15 years since the creation of the PNPMF, there was no appreciation of biodiversity and traditional knowledge, as most herbal medicines sold in Brazil are made from exotic or adapted species. here was no encouragement for the creation or permanence of Brazilian companies, as Anvisa s requirements do not favor them, the number of scientific researches with native species is limited and there is not enough money for the development of these programs in primary health careunits, as it does not there is a law that makes investments viable for this. Regarding the transformation and offer of other forms of care, self-care and self-attention, it does not happen, as the programs use more industrialized herbal medicines, following the molds of modern, prescriptive and symptom-focused medicine, with knowledge of species and use, therefore of the connection with this practice of care with autonomy and self-attention linked to the lack of access to medical services.