Les pathologies infectieuses, maladies causées par certains micro-organismes pathogènes parmi les bactéries, les virus, les champignons et les protozoaires, sont à l’origine des taux de mortalité et de morbidité élevés enregistrés surtout dans les pays en voie de développement où la majorité de la population n’a pas les moyens d'accéder aux soins de santé. Les résistances des micro-organismes aux antimicrobiens, observées actuellement dans la pratique médicale moderne, constituent un autre grand problème lié au traitement de ces maladies. Elles constituent l’une des menaces de santé les plus sérieuses et peuvent frapper n’importe qui dans le monde. Face à ces fléaux, il est urgent de découvrir de nouveaux agents antimicrobiens qui pourraient, éventuellement, présenter de nouveaux mécanismes d'action. Une bonne part des plantes utilisées en médecines traditionnelles contiennent des composants antimicrobiens utiles contre les infections et qui peuvent aider dans la lutte contre les maladies infectieuses liées à l’antibiorésistance. C’est dans cette optique que nous avons mené une enquête ethnobotanique sur les plantes médicinales utilisées contre les infections microbiennes en médecine traditionnelle Burundaise. Nous en avons inventorié 155 et sélectionné 5 d'entre elles (Justicia subsessilis Oliv. (Acanthaceae); Platostoma rotundifolium (Briq.) A. J. Paton (Lamiaceae), Virectaria major (Schum.) Verdc. (Rubiaceae), Pavetta ternifolia (Oliv.) Hiern (Rubiaceae), et Stomatanthes africanus (Oliv. & Hiern) R. M. King & H. Rob. (Asteraceae)) pour en étudier la composition phytochimique et les propriétés biologiques. Les extraits de ces plantes ont été évalués notamment pour leurs effets antibactériens direct (bactéricide ou bactériostatique) et indirect (modulation des mécanismes de résistance qui augmente ou restaure l’activité des antibiotiques sur des souches résistantes). Les cinq plantes retenues ont montré une activité antibactérienne, justifiant ainsi leur usage contre les infections microbiennes en médecine traditionnelle Burundaise et, plus particulièrement, l’espèce Platostoma rotundifolium, dont les extraits ont montré des effets antibactériens directs et indirects sur des souches sensibles et résistantes. Les extraits de Platostoma rotundifolium ont également présenté des effets sur l’expression de gènes (lasB et rhlA) impliqués dans le quorum sensing, et sur la formation du biofilm de Pseudomonas aeruginosa PAO1. En vue d’isoler et identifier les molécules responsables de ces différentes activités, l’extrait acétate d’éthyle (le plus actif) de Platostoma rotundifolium a été soumis à un fractionnement bioguidé. Celui-ci a permis d’isoler neuf composés qui ont été identifiés comme étant les acides ursolique, corosolique, tormentique, hyptadiénique, et 2α, 3α, 19β-trihydroxyurs-12-èn-28-oïque (isolé pour la première fois lors de ce travail et auquel nous avons donné le nom d’acide jérémique), le squalène, le cassipourol, le β-sitostérol et l’α-amyrine. Toutes ces molécules sont isolées pour la première fois de Platostoma rotundifolium. Les trois premiers composés ont présenté un effet bactéricide sur les souches bactériennes sensibles et résistantes, tandis que les trois derniers ont montré une action inhibitrice significative de l’expression de gènes (lasB et rhlA) impliqués dans le quorum sensing et de la formation de biofilm de Pseudomonas aeruginosa PAO1. Toutes ces molécules actives peuvent constituer une voie dans la lutte contre les maladies infectieuses et l’antibiorésistance; nous pouvons conclure que les données issues d’une enquête ethnobotanique sur les savoirs et les savoir-faire des guérisseurs traditionnels sont très importantes, surtout lorsqu’elles sont exploitées jusqu’à la détermination des principes actifs responsables d'une activité pharmacologique donnée. / Infectious pathologies are diseases caused by the transmission of some pathogenic microorganisms among bacteria, viruses, fungi and protozoa. They drive the high mortality and morbidity rates recorded especially in developing countries, where the majority of the population cannot afford to access health care. The antimicrobial resistances currently observed in modern medical practice represent another major problem in the treatment of these diseases. These resistances are one of the most serious population health threats and can strike anyone in the world. It has thus become urgent to discover new antimicrobial agents that could possibly have novel mechanisms of action.Many plants used in traditional medicines against infections harbor useful antimicrobial components that can help in the fight against infectious diseases and antibiotic resistances. In this context, we conducted an ethnobotanical survey of medicinal plants used in Burundian traditional medicine to treat microbial infections. We inventoried 155 herbs from which 5 (Justicia subsessilis Oliv. (Acanthaceae); Platostoma rotundifolium (Briq.) A. J. Paton (Lamiaceae), Virectaria major (Schum.) Verdc. (Rubiaceae), Pavetta ternifolia (Oliv.) Hiern (Rubiaceae), and Stomatanthes africanus (Oliv. & Hiern) R. M. King & H. Rob. (Asteraceae) were selected for phytochemical screening and biological assays. The extracts of these plants were evaluated for their antibacterial effects, direct (bacteriostatic or bactericidal) and indirect (inhibition of resistance mechanisms by increasing or restoring the activity of antibiotics against resistant strains). All the selected plants species have shown antibacterial activity, justifying their use against microbial infections in Burundian traditional medicine, and more particularly Platostoma rotundifolium, whose extracts showed direct and indirect antibacterial effects on susceptible and resistant (MRSA) strains. The extracts from Platostoma rotundifolium also presented inhibitory effects on the expression of genes involved in quorum sensing, lasB and rhlA, as well as on biofilm formation by Pseudomonas aeruginosa PAO1.In order to isolate and identify the molecules responsible for these activities, the ethyl acetate extract (most active) from Platostoma rotundifolium was submitted to bioguided fractionation. This led to the isolation of nine compounds that were identified as ursolic acid, corosolic acid, tormentic acid, hyptadienic acid and 2α, 3α, 19β-trihydroxyurs-12-en-28-oic acid (isolated for the first time during this work and that was named jeremic acid), squalene, cassipourol, β-sitosterol and α-amyrin. All these molecules were isolated for the first time from Platostoma rotundifolium. The first three compounds showed a bactericidal effect on sensitive and resistant strains of bacteria, while the last three showed significant inhibitory effects on the expression of two QS genes (lasB and rhlA), and on biofilm formation by Pseudomonas aeruginosa PAO1. All these active molecules can be a lead in the fight against antibiotic resistance; and we can conclude that the data from an ethnobotanical survey of the knowledge and skills of traditional healers are very important, especially when they are exploited until the determination of the active ingredients responsible for a specific pharmacological activity. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished

Plinia edulis (Myrtaceae), espécie arbórea popularmente conhecida como cambucá, é nativa da Mata Atlântica brasileira. Apesar do emprego na medicina tradicional em diversas moléstias, incluindo distúrbios gástricos, não existem estudos relacionando as atividades biológicas e os constituintes químicos da espécie. Esta tese relata a avaliação da gastroproteção, da atividade antioxidante, da citotoxicidade e da mutagenicidade do extrato etanol/água de folhas de P. edulis e das frações. Com o objetivo de correlacionar os metabólitos secundários com a eficácia da droga vegetal na medicina tradicional, o extrato foi submetido à partição e posterior fracionamento cromatográfico. O extrato apresentou atividade gastroprotetora significativa em modelo de indução de úlceras por etanol acidificado em ratos em doses de 100, 200 e 400 mg/kg via oral, sendo mais ativo que o fármaco de referência lansoprazol. Entre as frações, a hexânica (100 mg/kg p.o.) foi a mais eficaz, mas apresentou menor atividade do que o extrato bruto. A gastroproteção do ácido ursólico também foi avaliada, mas embora outros triterpenos sejam conhecidos como gastroprotetores, o ácido ursólico (50 mg/kg p.o.) reduziu a área lesionada, mas não apresentou atividade significativa no modelo empregado. O extrato não evidenciou mutagenicidade na concentração de 20 mg/placa no Ensaio de Ames e apresentou atividade antioxidante pronunciada, com CE50 de 5,75 µg/mL no ensaio com DPPH e valor de ORAC de 3.948 µmol de Trolox/g de extrato. O extrato e as frações foram avaliados quanto à citotoxicidade em linhagens de células tumorais humanas de UACC62 (melanoma), MCF-7 (mama), NCI 460 (pulmão), OVCAR03 (ovário), PC-03 (próstata), HT-29 (cólon), 786-0 (rins), NCI-ADR (mama com fenótipo de resistência a múltiplos fármacos) e linhagem de células normais de ovário de hamster chinês (CHO) in vitro. O extrato e as frações apresentaram citotoxicidade seletiva dose-dependente em células cancerígenas e atividade proliferativa em células normais. A partir das frações de hexano e acetato de etila foram identificados β-amirina, lupeol, β-sitosterol, ácido oleanólico, ácido ursólico, ácido maslínico, ácido corosólico, galato de etila, ácido gálico, quercitrina, miricitrina e quercetina por meio de análises espectrométricas. Estes resultados dão suporte à utilização popular desta espécie e estão provavelmente associados à presença dos flavonóides e triterpenos identificados no extrato. / Plinia edulis (Myrtaceae), an arboreous species popularly known as cambucá, is native in Brazilian Atlantic Rain Forest. Despite its traditional uses in many diseases, which include gastric disorders, no reports are available on the relationship between the biological activities of its extract and its chemical constituents. This thesis reports the evaluations of the the aqueous ethanol extract of leaves of P. edulis and its fractions on gastroprotective effect, antioxidant capacity, cytotoxicity and mutagenicity of. In order to correlate the secondary metabolites and the efficacy of the crude drug in traditional medicine, the extract was submitted to solvent partition followed by chromatographic fractionation. The extract exhibited significant gastroprotective effect on HCl/ethanol-induced ulcers in rats at doses of 100, 200 and 400 mg/kg p.o., even more active than the reference drug lansoprazole. Among the fractions, the hexane fraction (100 mg/kg p.o.) was the most effective, but showed lower activity than the crude extract. In addition, the gastroprotective effect of ursolic acid was evaluated. Although others triterpenes are well known as gastroprotective agents, ursolic acid (50 mg/kg p.o.) reduced the lesion area, but did not show significant activity on this model. The extract did not show mutagenicity at the concentration of 20 mg/plate in the Ames test and exhibited high antioxidant activity, with EC50 of 5.75 µg/mL on the DPPH assay and ORAC value of 3948 µmol Trolox/g of extract. The extract and its fractions were evaluated for cytotoxic activity against human tumour cell lines as UACC62 (melanoma), MCF-7 (breast), NCI 460 (lung, non-small cells), OVCAR03 (ovarian), PC-03 (prostate), HT-29 (colon), 786-0 (renal), NCI-ADR (breast expressing phenotype multiple drugs resistance) and CHO (Chinese Hamster Ovary) normal cell line in vitro. The extract and its fractions showed selectively dose-dependent cytotoxicity against cancer cells and proliferative activity in normal cells. The hexane and ethyl acetate fractions yielded β-amyrin, lupeol, β-sitosterol, oleanolic acid, ursolic acid, maslinic acid, corosolic acid, ethyl gallate, gallic acid, quercitrin, myricitrin and quercetin, which were identified based on spectrometric analyses. These results provide scientific support to the traditional use of this species, which are probably associated with the flavonoids and triterpenoids identified in the extract.

Dans le present travail de recherche notre équipe s'est interessé à l'étude de la composition chimique -au niveau moléculaire- d'un groupe d'échantillons résineuses provenant d'objects Aztecs et Mayas. Le but ultime de cette étude a été d'établir l'origin botanique de ces résines et d'avoir une vue d'ensemble des formulations utilisées dans les adhésifs ou les figurines, afin de mieux comprendre leurs propriétes physiques.Pour aboutir à cet objectif une stratégie analytique très spécifique a été créeé et mise en oeuvre. Cette stratégie a inclus l'analyse d'échantillons des résines archéologiques mais aussi de résines d'origine botanique certifiée et de résines commerciales, achetées dans des marchés traditionels au Mexique dans une région qui correspond a la one géographique occupée autre fois par l'empire aztèque.L'étude des matériaux a fait appel à des techniques tels que l'observation a l'échelle microscopique, la spectroscopie infrarouge (IRTF), la chromatographie liquide-DAD (HPLC-UV/Vis) et la chromatographie en phase gazeuse couplée à la spéctroscopie de masse (CPG-SM).L'étude moléculaire de ces échantillons, et plus précisement, l'étude leur fraction tritérpenique a permis de : Établir un profil moléculaire des résines pour chaque origine botanique étudiée Idéntifier précisement certain composées tritérpeniques présents dans toutes les échantillons Réperer les molécules tritérpeniques susceptibles d'être utilisées dans l'avenir comme des marqueurs moléculaires d'origine botanique pour les résines frais des espèces étudiées Suggèrer une origine botanique pour les échantillons archéologiques Aztèques Écarter des origines botaniques possibles pour l'échantillon Maya Avoir une vue d'ensemble de l'origine botanique des résines commercialisées au territoire mexicain sous le nom de «copal» Créer un protocole d'analyse simple pour permettre aux professionnels de la conservation et des biomatériaux d'établir l'origine botanique et un profil moléculaire des résines utilisées dans des expériences diverses Caractériser le comportement du copal lors du vieillisement naturel et artificiel Établir des molécules susceptibles de devenir marqueurs moléculairs pour les deux types de vieillisement Établir que l'origine botanique d'un échantillon résineux peut être retrouvée malgré son âge (archéologique) / In the present work, the molecular composition of series of resinous aztec and maya archaeological samples were investigated to determinate their nature.Thus an analytical strategy was specifically designed. This analytical strategy included the analysis of botanically certified resins, freshly collected. It included as well the analysis of commercial samples bought in Mexican traditional markets.The study of all the samples included microscopical techniques, Fourier Inverse Infrared Spectrometry (FTIR) , High Performance Liquid Chromatography coupled to Ultraviolet-visible spectrometry (HPLC-UV/Vis) and Gas Chromatography coupled to Mass Spectrometry (GC-MS).The molecular study of these samples, in particular of their trterpenic composition allowed to : establish the molecular profile of resins from certified botanical origin. Identifiy some of the triterpenic compounds present in samples; Identify triterpenic molecules that could be uses as molecular markers for each botanical origin. Find the botanical origin of archeological astec samples. Discard possible botanic origins for maya archaeological sample. Have an overview of the origin of commercial samples of mexican copal. Create a simple protocol that allows conservation and biomaterials professionals to establish the botanical origin of archaeological and commercial resins, used in conservation interventions. Observe the behavior of copal materials upon ageing, establishing potential markers for natural ageing in copal, under darkness. Asses the botanical origin of a sample can be found regardless the age of the resin

Plinia edulis (Myrtaceae), espécie arbórea popularmente conhecida como cambucá, é nativa da Mata Atlântica brasileira. Apesar do emprego na medicina tradicional em diversas moléstias, incluindo distúrbios gástricos, não existem estudos relacionando as atividades biológicas e os constituintes químicos da espécie. Esta tese relata a avaliação da gastroproteção, da atividade antioxidante, da citotoxicidade e da mutagenicidade do extrato etanol/água de folhas de P. edulis e das frações. Com o objetivo de correlacionar os metabólitos secundários com a eficácia da droga vegetal na medicina tradicional, o extrato foi submetido à partição e posterior fracionamento cromatográfico. O extrato apresentou atividade gastroprotetora significativa em modelo de indução de úlceras por etanol acidificado em ratos em doses de 100, 200 e 400 mg/kg via oral, sendo mais ativo que o fármaco de referência lansoprazol. Entre as frações, a hexânica (100 mg/kg p.o.) foi a mais eficaz, mas apresentou menor atividade do que o extrato bruto. A gastroproteção do ácido ursólico também foi avaliada, mas embora outros triterpenos sejam conhecidos como gastroprotetores, o ácido ursólico (50 mg/kg p.o.) reduziu a área lesionada, mas não apresentou atividade significativa no modelo empregado. O extrato não evidenciou mutagenicidade na concentração de 20 mg/placa no Ensaio de Ames e apresentou atividade antioxidante pronunciada, com CE50 de 5,75 µg/mL no ensaio com DPPH e valor de ORAC de 3.948 µmol de Trolox/g de extrato. O extrato e as frações foram avaliados quanto à citotoxicidade em linhagens de células tumorais humanas de UACC62 (melanoma), MCF-7 (mama), NCI 460 (pulmão), OVCAR03 (ovário), PC-03 (próstata), HT-29 (cólon), 786-0 (rins), NCI-ADR (mama com fenótipo de resistência a múltiplos fármacos) e linhagem de células normais de ovário de hamster chinês (CHO) in vitro. O extrato e as frações apresentaram citotoxicidade seletiva dose-dependente em células cancerígenas e atividade proliferativa em células normais. A partir das frações de hexano e acetato de etila foram identificados β-amirina, lupeol, β-sitosterol, ácido oleanólico, ácido ursólico, ácido maslínico, ácido corosólico, galato de etila, ácido gálico, quercitrina, miricitrina e quercetina por meio de análises espectrométricas. Estes resultados dão suporte à utilização popular desta espécie e estão provavelmente associados à presença dos flavonóides e triterpenos identificados no extrato. / Plinia edulis (Myrtaceae), an arboreous species popularly known as cambucá, is native in Brazilian Atlantic Rain Forest. Despite its traditional uses in many diseases, which include gastric disorders, no reports are available on the relationship between the biological activities of its extract and its chemical constituents. This thesis reports the evaluations of the the aqueous ethanol extract of leaves of P. edulis and its fractions on gastroprotective effect, antioxidant capacity, cytotoxicity and mutagenicity of. In order to correlate the secondary metabolites and the efficacy of the crude drug in traditional medicine, the extract was submitted to solvent partition followed by chromatographic fractionation. The extract exhibited significant gastroprotective effect on HCl/ethanol-induced ulcers in rats at doses of 100, 200 and 400 mg/kg p.o., even more active than the reference drug lansoprazole. Among the fractions, the hexane fraction (100 mg/kg p.o.) was the most effective, but showed lower activity than the crude extract. In addition, the gastroprotective effect of ursolic acid was evaluated. Although others triterpenes are well known as gastroprotective agents, ursolic acid (50 mg/kg p.o.) reduced the lesion area, but did not show significant activity on this model. The extract did not show mutagenicity at the concentration of 20 mg/plate in the Ames test and exhibited high antioxidant activity, with EC50 of 5.75 µg/mL on the DPPH assay and ORAC value of 3948 µmol Trolox/g of extract. The extract and its fractions were evaluated for cytotoxic activity against human tumour cell lines as UACC62 (melanoma), MCF-7 (breast), NCI 460 (lung, non-small cells), OVCAR03 (ovarian), PC-03 (prostate), HT-29 (colon), 786-0 (renal), NCI-ADR (breast expressing phenotype multiple drugs resistance) and CHO (Chinese Hamster Ovary) normal cell line in vitro. The extract and its fractions showed selectively dose-dependent cytotoxicity against cancer cells and proliferative activity in normal cells. The hexane and ethyl acetate fractions yielded β-amyrin, lupeol, β-sitosterol, oleanolic acid, ursolic acid, maslinic acid, corosolic acid, ethyl gallate, gallic acid, quercitrin, myricitrin and quercetin, which were identified based on spectrometric analyses. These results provide scientific support to the traditional use of this species, which are probably associated with the flavonoids and triterpenoids identified in the extract.