The present work describes the phytochemistry study and of biological activity of the species Scutellaria racemosa Pers (Labiatae) and Pfaffia tuberosa Spreng (Amaranthaceae). Four compounds were isolated of the S. racemosa Pers: lupeol (14), oroxilin A (10), dinatin (12) and oroxyloside (11). The antimicrobial and cytotoxic activities and the capacity of inhibition of enzymes prolyl oligopeptidase (POP), dipeptidyl peptidase IV (DPP IV) and acetylcholinesterase (AChE) of the crude extract (EB), fractions and isolated compounds of the S. racemosa Pers were evaluated. The n-hexane (FH) and ethyl acetate (FA) fractions were the most active against Staphylococcus epidermidis, Bacillus subtilis and Pseudomonas aeruginosa. The evaluation of the crude extract and fractions using the Brine Shrimp Lethality Test indicated that this plant does not present toxicity. About the tests of enzymatic inhibition, the ethyl acetate (FA) and n-butanol (FB) fractions of S. racemosa Pers and the compounds dinatin (12) and oroxyloside (11) demonstrated significant capacity of inhibition of the POP. The inhibition promoted for the dinatina (12) (100 μM) corresponded 43% and for the oroxyloside (11) (100 μM) corresponded 34% of the total enzyme tested. The crude extract (EB) and the respective fractions of the Pfaffia tuberosa Spreng were also evaluated about the antimicrobial and cytotoxic activities and of enzymatic inhibition of the POP, DPP IV and AChE. Through these assays, it was verified that the crude extract (EB) and the fractions of the Pfaffia tuberosa Spreng do not present important antimicrobial and cytotoxic activity. In relation to the tests of inibitory activity of the POP, the dichloromethane (FD) and ethyl acetate (FA) fractions present IC50 of 21.4 and 28.5 μg/mL against of POP, respectively. Dichloromethane, ethyl acetate and n-butanol fractions (FD, FA and FB) presented low activity against DPP IV (< 20%). The ethyl acetate (FA) and n-butanol (FB) fractions showed significant inhibition of the AChE in the amounts, 6.25 and 25 μg, respectively. / O presente trabalho descreve o estudo fitoquímico e a atividade biológica das espécies Scutellaria racemosa Pers (Labiatae) e Pfaffia tuberosa Spreng (Amaranthaceae). Quatro compostos foram isolados da S. racemosa Pers: lupeol (14), oroxilina A (10), dinatina (12) e oroxilosídeo (11). A atividade antimicrobiana, citotóxica e a capacidade de inibição das enzimas prolil oligopeptidase (POP), dipeptidil peptidase IV (DPP IV) e acetilcolinesterase (AChE) do extrato bruto (EB), frações e compostos isolados da S. racemosa Pers foram avaliadas. As frações n-hexano (FH) e acetato de etila (FA) foram as mais ativas contra Staphylococcus epidermidis, Bacillus subtilis e Pseudomonas aeruginosa. A avaliação do extrato bruto (EB) e frações através do teste de letalidade frente a Artemia salina indicou que esta planta não apresenta toxicidade significativa. Quanto aos testes de inibição enzimática, as frações acetato de etila (FA) e n-butanol (FB) de S. racemosa Pers e os compostos dinatina (12) e oroxilosídeo (11) demonstraram significativa capacidade de inibição da POP. A inibição promovida pela dinatina (12) (100 μM) correspondeu a 43% e pelo oroxilosídeo (11) (100 μM) correspondeu a 34% do total de enzima testada. O extrato bruto (EB) e as respectivas frações da Pfaffia tuberosa Spreng também foram avaliadas quanto a atividade antimicrobiana, citotóxica e de inibição enzimática da POP, DPP IV e AChE. Através destes ensaios, verificou-se que o extrato bruto (EB) e a frações da Pfaffia tuberosa Spreng não apresentam importante atividade antimicrobiana e citotóxica. Em relação aos testes de atividade inibitória da POP, as frações diclorometano (FD) e acetato de etila (FA) foram as que apresentaram os melhores resultados, com IC50 de 21,4 e 28,5 μg/mL, respectivamente. As frações diclorometano, acetato de etila e n-butanol (FD, FA e FB) apresentaram baixa capacidade de inibição da DPP IV (< 20%). As frações acetato de etila (FA) e n-butanol (FB) apresentaram significativa inibição da AChE, nas quantidades de 6,25 e 25 μg, respectivamente.

No description available.

Eine ständig steigende Nachfrage nach einer auf pflanzlichen Stoffen basierenden Hormonersatztherapie für menopausale Beschwerden, macht eine verstärkte Untersuchung sogenannter Phytoöstrogene erforderlich. Bei den hier untersuchten Substanzen handelt es sich um die chemisch synthetisierten Flavanone 6-(1,1-Dimethylallyl)Naringenin (6DMAN) und 8-Prenylnaringenin (8PN), die ursprünglich in Pflanzen identifiziert wurden. 7-Oxyprenylnaringenin-4'-Azetat (7OPN) ist ein weiteres Mitglied dieser Stoffgruppe, zu dem jedoch bisher noch praktisch keine Daten vorlagen. Ebenfalls in die Untersuchungen einbezogen wurde ein isopropanolischer Extrakt aus dem Rhizom von Cimicifuga racemosa (L.) Nutt. (iCR), der schon seit langer Zeit erfolgreich zur Bekämpfung menopausaler Beschwerden eingesetzt wird, dessen Wirkmechanismus jedoch unbekannt ist und zu dem bisher noch wenige molekulare Daten bezüglich der Wirkung auf einzelne Zielorgane, insbesondere nach einer Behandlung über einen längeren Zeitraum vorliegen. Die durchgeführten Untersuchungen betrafen zum Einen den Uterus als eines der Hauptzielorgane weiblicher Sexualhormone und zum Anderen die Vena cava, repräsentativ für das Gefäßsystem. Als Modellorganismus wurden Ratten gewählt. Dabei wurde die Genexpression Östrogen (E2)-regulierter Gene auf mRNA-Ebene mittels Real-Time-PCR bestimmt. Die Wirkung von 7OPN wurde in einem in vitro-System (MVLN-Zellen) und im Uterus getestet. Zusätzlich wurden humane Nabelschnurvenen-Endothelzellen als in vitro-Modell für das Gefäßsystem eingesetzt. Mit ihnen wurde die Wirkung der Testsubstanzen auf Angiogenese und Differenzierung getestet. Die durch die E2 hervorgerufenen Effekte entsprachen weitestgehend den Erwartungen. Es konnte sowohl eine Zunahme des Uterusgewichts der Ratten als auch eine Regulation der Expression von Proliferationsmarkern und E2-abhängig regulierten Genen im Uterus auf mRNA-Ebene festgestellt werden. Auch im Gefäßsystem konnte sowohl eine Regulation E2-abhängig exprimierter Gene beobachtet werden, als auch ein proliferationsfördernde und differentiationsfördernde Wirkung auf venöse Endothelzellen in vitro. Die untersuchten Flavanone zeigten einen von den vorhandenen funktionalen Gruppen abhängigen Effekt auf die E2-regulierten Prozesse und Gene. Während es sich bei 8PN um eine rein östrogen wirkende Substanz zu handeln scheint, wirkt 6DMAN offenbar als selektiver Östrogenrezeptor-Modulator (SERM) und zeigt für einen Einsatz in der HRT sehr interessante Eigenschaften, da weder ein uterotrophe Wirkung in vivo, noch eine angiogene Wirkung in vitro beobachtet werden konnte, während gleichzeitig eine östrogene, potentiell kardioprotektive Wirkung auf die Genexpression im Gefäßsystem gezeigt werden konnte. Auch 7OPN zeigt ein differenziertes Wirkmuster. Ein in vitro-Reportergentest in einer stabil transfizierten Brustkrebszellinie deutete auf eine in Abhängigkeit von der Konzentration E2-antagonistische oder agonistische Wirkung hin. Die Genexpressionsstudien im Uterus der Versuchstiere nach dreitägiger Behandlung zeigten, daß die Wirkung von 7OPN jedoch auch abhängig vom untersuchten Gen ist. Da auch dieses Flavanon keine uterotrophe Wirkung zu besitzen scheint, ist 7OPN ebenfalls eine interessante Zielsubstanz weiterer Untersuchungen im Hinblick auf die Anwendung in der HRT. Für den in einem Arzneimittel enthaltenen Extrakt iCR konnte in einem 17-tägigen Tierversuch keine östrogene Wirkung auf Uterus und Gefäßsystem gezeigt werden. Während eine Anwendung dieses Extrakts zur Behandlung menopausaler Beschwerden im Lichte dieser Ergebnisse und langjähriger praktischer Erfahrungen zwar sicher erscheint, bleibt der Wirkmechanismus von iCR weiterhin unbekannt.

Plant–animal interaction systems are complex food webs where the members—plants, pollinators, herbivores, parasites and predators of the pollinators/herbivores—interact with each other in ways which maximize their own fitness. Based on the net outcome, such interactions could be mutually beneficial to the interacting members (mutualism) or beneficial to only one of the interacting members at the cost of the other interacting members (herbivory, predation, parasitism). It is possible that such outcomes are actually a continuum and could swing in either direction from beneficial to detrimental and vice versa. Such transitions happen not only over long time scales, but could also happen within shorter time scales based on conditionalities. Conditional outcomes are those in which the outcome of an interaction between two partners is conditional on the involvement of a third partner. Thus, studying such outcomes necessitates taking into account systems beyond the classical two-partner interactions. In such complex multitrophic plant–animal interaction systems in which there are direct and indirect interactions between species, comprehending the dynamics of these multiple partners is very important for an understanding of how the system is structured. In Chapter 2 we investigate Ficus racemosa and its community of obligatory mutualistic and parasitic fig wasps that develop within the fig inflorescence or syconium, as well as their interaction with opportunistic ants. We focus on temporal resource partitioning among members of the fig wasp community over the development cycle of the fig syconia during which wasp oviposition and development occur and we study the activity rhythm of the ants associated with this community. We found that the members of the wasp community partitioned their oviposition across fig syconium development phenology and showed interspecific variation in activity across the diel cycle. The wasps presented a distinct sequence in their arrival at fig syconia for oviposition. We documented night oviposition in several fig wasp species for the first time. Ant activity on the fig syconia was correlated with wasp activity and was dependent on whether the ants were predatory or trophobiont-tending species; only numbers of predatory ants increased during peak arrivals of the wasps. In Chapter 3, we found that predatory ants (Oecophylla smaragdina) patrolling F. racemosa trees were attracted to the odour from fig syconia at different developmental phases, as well as to the odours of fig wasps, whereas other predatory ants (Technomyrmex albipes) responded only to odours of syconia from which fig wasps were dispersing and to fig wasp odour. However, trophobiont-tending ants (Myrmicaria brunnea) patrolling the same trees and exposed to the same volatiles were unresponsive to fig or fig wasp odours. The predatory ants demonstrated a concentration-dependent response towards volatiles from figs receptive to pollinators and those from which wasps were dispersing while the trophobiont-tending ants were unresponsive to such odours at all concentrations. Naıve predatory ants failed to respond to the volatiles to which the experienced predatory ants responded, indicating that the response to fig-related odours is learned. In Chapter 4 we characterise the dynamics of the volatile bouquet of the fig syconium from the initiation through pre-receptive, receptive, and late inter-floral stages which act as signals/ cues for different fig wasp species. We were also interested in diel patterns of volatile emission as some fig wasp species were strictly diurnal (the pollinator, Ceratosolen fusciceps) whereas other fig wasps such as Apocryptophagus fusca were observed ovipositing even during the nocturnal hours. We identified volatiles that were specific to syconium development phase as well as to the time of day in this bouquet. α-muurolene was identified as the sesquiterpene specific to receptive-phase as well as being present only during the day thus coinciding with the diurnal pollinator arrival pattern. Volatiles such as (E)-β-ocimene were present in increasing levels across the developmental stages of the fig and thus could act as background volatiles providing suitable information to fig wasps about host plants and their phases. Chapter 5 examines the responses of predatory and trophobiont-tending ant species to the cuticular hydrocarbon (CHC) extracts of four galler and two parasitoid fig wasp species associated with F. racemosa. Interestingly, the antennation response of both experienced and na¨ıve ants to these wasp extracts was identical indicating that prior exposure to such compounds is not necessary for eliciting such response. We also characterised these cuticular hydrocarbon extracts to find potential compounds which could as short-range cues for predatory ants. Ants were more responsive to the cuticular extracts of parasitoids rather than to those of galler wasps, implying that the CHC profile of carnivorous prey may contain more elicitors of aggressive behaviour in ants compared to herbivorous prey whose profiles may be more similar to those of their plant resources. We also find congruency between the cuticular profiles of parasitoids and their hosts suggesting that parasitoids could sequester compounds from their diet. Important findings and conclusions of the thesis are presented in Chapter 6. The first two parts of the appendices section discuss work carried out on alternative ways of analysing multivariate data sets such as plant volatiles and insect cuticular hydrocarbons. Appendix A details the use of Random Forests, an algorithm-based method of analysing complex data sets where there are more variables than samples, a situation akin to microarray data sets. This work illustrates the use of such techniques in chemical ecology, highlighting the potential pitfalls of classical multivariate tests and the advantages of newer more robust methods. Appendix B, an invited article following the publication of the earlier work, compares different data transformation procedures currently employed in such multivariate analysis. Appendix C details sex-specific differences in cuticular hydrocarbons of fig wasps, using the pollinator C. fusciceps as a case study.

Mangrove ecosystems are found in tropical coastal areas and play vital roles in shoreline protection, habitat support, and medicinal value. These ecosystems are under threat from human activities and climate change. This thesis explored the biodiversity and evolutionary ecology of mangroves in the Indonesian Archipelago, home to the world’s richest composition of mangrove species. Indonesia's geography, including over 17,500 islands and the intersection of Laurasian and Gondwanan flora, makes it an ideal location for studying mangrove evolution. Sea level changes and the presence of land and oceanic barriers have shaped the distribution and evolution of mangroves, with the Indonesian Throughflow (ITF) playing an essential role in genetic exchange. The study analyzed 14 populations of Lumnitzera littorea and 21 populations of L. racemosa, utilizing DNA sequencing to assess genetic diversity, structure, and dispersal in relation to geographical distance and sea surface currents. Both species showed low genetic variation, and significant effects of distance and sea current connectivity were observed. Sulawesi acted as a barrier in genetic differentiation, while other barriers were discovered affecting population structure. Divergent evolutionary trajectories were noted between L. littorea and L. racemosa. The study also investigated the relationship between phylogeny and the chemophenetic patterns of their natural products, given their anti-microbial, antioxidant, and other properties. Techniques such as chromatographic separation and high-resolution ESI-MS were used to link molecular phylogeny with phytochemical characterizations. Root samples were collected for chemical analysis, revealing an unusual diversity in sulfated constituents, with some compounds found for the first time in mangroves. Specific geographical areas showed antibacterial potential, and a previously unknown compound, Lumnitzeralactone, was identified. The conclusion highlights this study as the first to reveal molecular evidence of intraspecific phylogroups in Lumnitzera mangroves, with distinctions defined by geographical lines such as Wallace's line. Additionally, the study found promising sources for anti-bacterial agents and potential therapeutic benefits to human health. The observed genetic differentiation emphasizes the need for conservation strategies at the population level, and the potential for new medicines underscores the importance of mangrove conservation in their natural habitats across Indonesia.:Preface 4 Summary 5 Zusammenfassung 10 1. Introduction 15 1.1. Characteristics, significance, and threat of mangroves 15 1.1.1. Characteristics of mangroves 15 1.1.2. Significance of Indonesian mangroves 16 1.1.3. Threats to mangroves 18 1.2. Evolutionary processes and diversity of mangroves 19 1.2.1. Evolution of mangroves 19 1.2.2. Sea surface currents in Indonesia shape genetic structure 20 1.2.3. The relevance of Wallace’s line to mangrove evolution 22 1.2.4. Isolation by geographical distance 24 1.2.5. Genetic diversity and population structure 25 1.3. Diversity of bioactive compounds of mangrove genus Lumnitzera 27 1.3.1. Sulfur-containing metabolites 27 1.3.2. Phylogenetics 28 1.3.3. Anti-infective potential 29 1.4. Study species 30 1.5. Aim of the thesis 33 2. Material and Methods 37 2.1. Sampling and sample design 37 2.2. Laboratory procedures and genetic analysis 38 2.2.1. DNA isolation 38 2.2.2. ddRADseq sequencing, and bioinformatics 38 2.2.3. Genetic diversity, population structure and differentiation 40 2.2.4. Identifying barriers and areas of connectivity 41 2.2.5. Isolation by distance and sea surface current connectivity 42 2.2.6. Polymerase Chain Reaction (PCR), and phylogenetic analyses 43 2.3. Laboratory procedures and phytochemical analysis 44 2.3.1. Root sample extraction 44 2.3.2. TLC, Low-resolution ESI-MS spectra, HPLC, and NMR 45 2.3.3. UHPLC-ESI-QqTOF-MS and MS/MS 46 2.3.4. RP-UHPLC-ESI-LIT-Orbitrap-MS 47 2.3.5. Extraction and isolation of compounds 47 2.3.6. Anti-infective bioassays 51 3. Results 52 3.1. Genetic diversity and population structure 52 3.1.1. Genetic diversity 52 3.1.2. Population structure and genetic differentiation 54 3.1.3. Effective migration 58 3.1.4. Isolation by distance and sea surface current connectivity 59 3.2. Unusual-sulfated constituent and anti-infective properties 61 3.2.1. Phytochemical screening 61 3.2.2. Phylogenetic tree of Lumnitzera 69 3.2.3. Evaluation of anti-infective properties 70 4. Discussion 74 4.1. Population genomics of Lumnitzera mangroves in Indonesia 74 4.1.1. The genetic diversity paradox in mangroves 74 4.1.2. Phylogroups and the Sunda-Wallacea biogeographical pattern 76 4.1.3. Limited mixture among phylogroups and populations by sea surface currents 78 4.1.4. Restricted gene flow by geographical distance 80 4.1.5. Evolutionary ecology of Lumnitzera inferred by genetics and chemodiversity 81 4.2. Bioactive compounds and anti-infective potential of Lumnitzera 82 4.2.1. Diversity of bioactive compounds 82 4.2.2. Sulfated and nonsulfated ellagic acid supported by phylogenetic pattern 83 4.2.3. Anti-infective properties and their restriction to particular locations 86 5. Conclusion and future perspective 89 6. References 94 7. Appendix 111 Curriculum vitae 119 Declaration of independent work 122 Acknowledgments 123 Author contributions statement 125 / Viele Mangrovenarten haben neben Holz- und Nichtholzprodukten auch einen medizinischen Wert und werden traditionell genutzt. Doch durch menschliche Aktivitäten und den Anstieg des Meeresspiegels durch den Klimawandel verschwinden sie rasch. Diese Arbeit erforscht die biologische Vielfalt der Mangroven im indonesischen Archipel, insbesondere die Arten Lumnitzera littorea und Lumnitzera racemosa. Der indonesische Archipel hat die weltweit reichste Mangrovenzusammensetzung und dient als Übergangsregion für verschiedene Pflanzenlinien. Der Meeresspiegelanstieg und dessen mögliche Auswirkungen auf Mangroven wurden genau untersucht. Mangroven besitzen schwimmfähige Fortpflanzungsorgane, und die Meeresströmungen des Indonesian Throughflow (ITF) könnten den genetischen Austausch zwischen verschiedenen Populationen ermöglichen. In der Studie wurden 14 Populationen von L. littorea und 21 von L. racemosa genotypisiert. Die Ergebnisse zeigten eine geringe genetische Variation auf Populationsebene und eine signifikante genetische Differenzierung, beeinflusst von Entfernung und Meeresströmung. Es wurden auch divergierende Entwicklungsverläufe und zwei Phylogruppen bei beiden Arten beobachtet. Die Studie untersuchte auch die phylogenetischen Beziehungen und die Chemophenetik der beiden Arten. Mangrovenböden weisen einen hohen Sulfatgehalt auf, und medizinisch wirksame Verbindungen werden oft von Mikroorganismen wie endophytischen Pilzen produziert. Schwefelverbindungen in Mangroven wurden bisher vernachlässigt. Durch Kombination von phylogenetischen Daten mit chemischen Analysen wurde die Entwicklung der Mangrovenarten und die Vielfalt der Wurzelmetaboliten untersucht. Es wurden chromatographische und tandemmassenspektrometrische Techniken eingesetzt, um eine molekulare Phylogenie mit phytochemischen Charakterisierungen zu verbinden. Die Untersuchung ergab eine ungewöhnliche Vielfalt an sulfatierten Bestandteilen und antibakterielles Potenzial. Zusammenfassend liefert die Studie molekulare Beweise für intraspezifische Phylogruppen in Lumnitzera-Mangroven, definiert durch die biogeografische Trennung von Sunda und Wallacea. Beide Arten stellen eine vielversprechende Quelle für antibakterielle Wirkstoffe dar, einschließlich sulfatierter Ellagsäurederivate. Die populationsgenomischen Ergebnisse liefern Informationen über die Erhaltungsstrategie von Lumnitzera-Arten, und die metabolomischen Ergebnisse berichten über potenzielle neue Arzneimittel, was die Bedeutung der Erhaltung von Mangroven in ihren natürlichen Lebensräumen im gesamten indonesischen Archipel unterstreicht.:Preface 4 Summary 5 Zusammenfassung 10 1. Introduction 15 1.1. Characteristics, significance, and threat of mangroves 15 1.1.1. Characteristics of mangroves 15 1.1.2. Significance of Indonesian mangroves 16 1.1.3. Threats to mangroves 18 1.2. Evolutionary processes and diversity of mangroves 19 1.2.1. Evolution of mangroves 19 1.2.2. Sea surface currents in Indonesia shape genetic structure 20 1.2.3. The relevance of Wallace’s line to mangrove evolution 22 1.2.4. Isolation by geographical distance 24 1.2.5. Genetic diversity and population structure 25 1.3. Diversity of bioactive compounds of mangrove genus Lumnitzera 27 1.3.1. Sulfur-containing metabolites 27 1.3.2. Phylogenetics 28 1.3.3. Anti-infective potential 29 1.4. Study species 30 1.5. Aim of the thesis 33 2. Material and Methods 37 2.1. Sampling and sample design 37 2.2. Laboratory procedures and genetic analysis 38 2.2.1. DNA isolation 38 2.2.2. ddRADseq sequencing, and bioinformatics 38 2.2.3. Genetic diversity, population structure and differentiation 40 2.2.4. Identifying barriers and areas of connectivity 41 2.2.5. Isolation by distance and sea surface current connectivity 42 2.2.6. Polymerase Chain Reaction (PCR), and phylogenetic analyses 43 2.3. Laboratory procedures and phytochemical analysis 44 2.3.1. Root sample extraction 44 2.3.2. TLC, Low-resolution ESI-MS spectra, HPLC, and NMR 45 2.3.3. UHPLC-ESI-QqTOF-MS and MS/MS 46 2.3.4. RP-UHPLC-ESI-LIT-Orbitrap-MS 47 2.3.5. Extraction and isolation of compounds 47 2.3.6. Anti-infective bioassays 51 3. Results 52 3.1. Genetic diversity and population structure 52 3.1.1. Genetic diversity 52 3.1.2. Population structure and genetic differentiation 54 3.1.3. Effective migration 58 3.1.4. Isolation by distance and sea surface current connectivity 59 3.2. Unusual-sulfated constituent and anti-infective properties 61 3.2.1. Phytochemical screening 61 3.2.2. Phylogenetic tree of Lumnitzera 69 3.2.3. Evaluation of anti-infective properties 70 4. Discussion 74 4.1. Population genomics of Lumnitzera mangroves in Indonesia 74 4.1.1. The genetic diversity paradox in mangroves 74 4.1.2. Phylogroups and the Sunda-Wallacea biogeographical pattern 76 4.1.3. Limited mixture among phylogroups and populations by sea surface currents 78 4.1.4. Restricted gene flow by geographical distance 80 4.1.5. Evolutionary ecology of Lumnitzera inferred by genetics and chemodiversity 81 4.2. Bioactive compounds and anti-infective potential of Lumnitzera 82 4.2.1. Diversity of bioactive compounds 82 4.2.2. Sulfated and nonsulfated ellagic acid supported by phylogenetic pattern 83 4.2.3. Anti-infective properties and their restriction to particular locations 86 5. Conclusion and future perspective 89 6. References 94 7. Appendix 111 Curriculum vitae 119 Declaration of independent work 122 Acknowledgments 123 Author contributions statement 125

Esta Dissertação apresenta informações gerais sobre os medicamentos fitoterápicos e os aspectos toxicológicos de uma amostra de dez plantas medicinais comercializadas como medicamentos fitoterápicos no Brasil, pesquisados junto aos principais bancos de dados e fontes públicas de informação. A análise dos medicamentos fitoterápicos cobre as dimensões histórica, econômica e farmacêutica. No tocante aos aspectos toxicológicos, foram avaliados os dados de toxicidade pré-clínica de dez plantas selecionadas, e realizado um levantamento das informações publicadas para Hypericum perforatum e Piper methysticum, relacionadas ao termo toxicidade, segundo três importantes bancos de dados. Adicionalmente, este trabalho aborda as propostas para realização de ensaios de toxicidade pré-clínica para os fitoterápicos segundo a OMS e legislação brasileira, e as normas para avaliação de substâncias químicas segundo a OECD. / This thesis presents general information on herbal medicines and on the toxicological aspects of a sample of ten medicinal plants traded as herbal medicines in Brazil. The survey was carried out in the main databases and public sources of information. The analysis on the herbal medicines encompasses the historical, economic and pharmaceutical dimensions. In what concerns toxicological aspects, data on pre-clinical toxicity were evaluated for Hypericum perforatum and Piper methysticum, these keywords being related to toxicity in three important databases. In addition, this study discusses the proposals for pre-clinical toxicity trials on herbal medicines according to WHO and the Brazilian legislation, and the standards for evaluation of chemical substances according to OECD.

Esta Dissertação apresenta informações gerais sobre os medicamentos fitoterápicos e os aspectos toxicológicos de uma amostra de dez plantas medicinais comercializadas como medicamentos fitoterápicos no Brasil, pesquisados junto aos principais bancos de dados e fontes públicas de informação. A análise dos medicamentos fitoterápicos cobre as dimensões histórica, econômica e farmacêutica. No tocante aos aspectos toxicológicos, foram avaliados os dados de toxicidade pré-clínica de dez plantas selecionadas, e realizado um levantamento das informações publicadas para Hypericum perforatum e Piper methysticum, relacionadas ao termo toxicidade, segundo três importantes bancos de dados. Adicionalmente, este trabalho aborda as propostas para realização de ensaios de toxicidade pré-clínica para os fitoterápicos segundo a OMS e legislação brasileira, e as normas para avaliação de substâncias químicas segundo a OECD. / This thesis presents general information on herbal medicines and on the toxicological aspects of a sample of ten medicinal plants traded as herbal medicines in Brazil. The survey was carried out in the main databases and public sources of information. The analysis on the herbal medicines encompasses the historical, economic and pharmaceutical dimensions. In what concerns toxicological aspects, data on pre-clinical toxicity were evaluated for Hypericum perforatum and Piper methysticum, these keywords being related to toxicity in three important databases. In addition, this study discusses the proposals for pre-clinical toxicity trials on herbal medicines according to WHO and the Brazilian legislation, and the standards for evaluation of chemical substances according to OECD.

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