This work describes the study chemical and pharmacological of the extracts and compounds isolated from two species of Rubiaceae (Sabicea grisea Cham. & Schltdl. var. grisea and Psychotria barbiflora DC.). Extracts and fractions of S. grisea, and fractions which showed positive reactions record to alkaloids of P. barbiflora, exhibited a significant reduction in the nociceptive response, with inhibition upper or comparable to the reference drug, indomethacin. The chemical study of fractions from leaves and stems of S. grisea, guided by pharmacological tests, resulted to the isolation of two saturated alcohols, octacosanol and hexacosanol, two pentacyclic triterpenes oleanane serie, siaresinolic and 3-O-α-L-rhamnopyranosyl-(1→2)-α-Larabinopyranosylsiaresinolic acids, vanillic and salicylic acids, scopoletin, ethyl caffeate and two phytosteroids, β-sitosterol and 3-O-β-D-glucopyranosylsitosterol. It is noteworthy that no previous reports about the presence of these compounds in the genus Sabicea. Moreover, no record was found on the 3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl-siaresinolic acid, named Gottliebside, an simple tribute to the greatest Natural Products Chemistry of the Brazil, Prof. Otto Richard Gottlieb, therefore, a new natural product. The chemical study of alkaloidal fractions from leaves and stems of P. barbiflora led to the isolation of two β-carboline alkaloids, harman and stricnosidinic acid, whose occurrences corroborate the inclusion of this species in the subgenus Heteropsychotria. In the pharmacological tests, octacosanol (10 and 1 mg/kg, i.p) and siaresinolic acid (1 and 0.1 mg/kg, i.p) showed peripheral antinociceptive effects mediated by α2-adrenergic receptors and channel K+ ATPdependent, respectively. Furthermore, these compounds inhibited the accumulation of inflammatory cells, as well as TNF-α in the model of carrageenan-induced inflammation, indicating an anti-inflammatory action. In addition, these compounds (≤200 μg/ml and ≤ 50 μg/ml, respectively) were unable to induce cell death in when evaluated in the reduction of 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, demonstrating the absence of cytotoxicity of these compounds. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Este trabalho descreve o estudo químico e farmacológico dos extratos e compostos isolados de duas espécies de Rubiaceae (Sabicea grisea Cham. & Schltdl. var. grisea e Psychotria barbiflora DC.). Extratos e frações de S. grisea, bem como frações com reações positivas para alcaloides obtidas de P. barbiflora, exibiram redução significativa da resposta nociceptiva, com inibição superior ou comparável ao fármaco de referência, indometacina. O estudo químico das frações das folhas e caule de S. grisea, guiados pelos ensaios farmacológicos, resultou no isolamento de dois alcoóis saturados, octacosanol e hexacosanol, dois triterpenos pentacíclicos da série oleanano, ácidos siaresinólico e 3-O-α-L-rhamnopiranosil-(1→2)-α-Larabinopiranosilsiaresinólico, os ácidos salicílico e vanílico, a escopoletina, o cafeato de etila, além dos fitoesteroides, o β-sitosterol e 3-O-β-D-glicopiranosilsitosterol. Não há relatos sobre a presença destes compostos no gênero Sabicea e não foi encontrado registro sobre o ácido 3-O-α-L-rhamnopiranosil-(1→2)-α-Larabinopiranosilsiaresinólico, nomeado de Gottliebsídeo, uma singela homenagem ao maior Químico em Produtos Naturais do Brasil, Prof. Otto Richard Gottlieb, sendo, portanto, um novo produto natural. O estudo químico das frações alcaloídicas das folhas e caule de P. barbiflora conduziu, pela primeira vez, ao isolamento de dois alcaloides β-carbolínicos, harmana e ácido estrictosidínico, cujas ocorrências corroboram com a inclusão desta espécie no subgênero Heteropsychotria. Nos ensaios farmacológicos, o octacosanol (10 e 1 mg/kg, i.p) e o ácido siaresinólico (1 e 0,1 mg/kg, i.p) apresentaram efeitos antinociceptivos periféricos mediado por receptores α2-adrenérgicos e canais de K+ATP-dependente, respectivamente. Além disso, estes compostos inibiram o acúmulo de células inflamatórias, bem como os níveis de TNF-α no modelo de inflamação induzida por carragenina, indicando uma ação anti-inflamatória. Em adição, o octacosanol (≤ 200 μg/ml) e o ácido siaresinólico (≤ 50 μg/ml) não foram capazes de induzir morte nas célula quando avaliados no teste de redução do brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT), revelando ausência de citotoxicidade destes compostos.

Le genre Psychotria est le plus vaste de la famille des Rubiaceae, avec plusieurs centaines d’espèces répandues dans toutes les régions tropicales humides. Les Psychotria sont principalement des arbustes (quelques-uns sont lianescents, herbacés ou arborescents) et entrent souvent pour une part importante dans la composition des sous-bois tropicaux. Certains montrent des adaptations remarquables comme la symbiose bactérienne foliaire ou l’accumulation d’humus. En raison de sa taille et des difficultés d’identifications, ce genre reste mal connu, notamment en Afrique occidentale et centrale où il n’a fait l’objet d’aucun travail d’ensemble depuis les années 1960.<p>Le présent travail a pour objectifs :1) la révision taxonomique du genre Psychotria pour l’Afrique occidentale et centrale; 2) une étude phylogénétique du genre, visant à reconstituer son évolution et améliorer la classification infragénérique ;et 3) une étude biogéographique régionale de ce groupe, afin de définir des centres de diversité et d'endémisme.<p>Notre travail de taxonomie, fondé sur l’examen des spécimens d’herbier et sur des missions de terrain au Cameroun et au Gabon, nous a conduit à reconnaître l’existence de 232 espèces en Afrique occidentale et centrale, ce qui fait de Psychotria le plus vaste genre de plantes dans cette région. Parmi ces espèces, 78 sont nouvelles.<p>Nos travaux phylogénétiques, basés sur l’étude de deux marqueurs nucléaires (ITS et ETS) et quatre chloroplastiques (rps16, trnG, matK et rbcLa), montrent que la classification de Petit (1964, 1966) est largement à revoir. Il apparaît notamment que les deux sous-genres (Psychotria et Tetramerae) reconnus en Afrique, et fondés sur la présence ou l’absence de nodules bactériens foliaires, ne sont pas monophylétiques, certaines espèces ayant secondairement perdu leurs nodules. Nos résultats soutiennent également le rattachement du genre monospécifique Peripeplus à Psychotria.<p>Le genre Psychotria montre une diversité remarquable, associée à un taux d’endémisme élevé, dans le domaine bas-guinéen (Cameroun et Gabon principalement) où plusieurs centres d’endémisme ont été identifiés. Ceux-ci sont localisés non seulement dans les massifs montagneux de l’intérieur, dont la flore particulière est bien connue, mais également dans les régions littorales. L’Afrique de l’ouest, moins diversifiée, montre cependant un fort endémisme localisé principalement dans deux centres, l’un situé au Liberia et dans l’ouest de la Côte d’Ivoire, l’autre vers la frontière Côte d’Ivoire/Ghana. Le bassin du Congo, comparable en diversité à l’Afrique de l’Ouest, est relativement pauvre en endémiques.<p>Ces résultats suggèrent que les forêts du Cameroun et du Gabon auraient relativement bien résisté aux périodes sèches passées, et remettent notamment en question l’hypothèse d’une disparition des forêts littorales du golfe de Guinée au cours du Pleistocène./Psychotria is the largest genus in the Rubiaceae family, with several hundred species in wet tropical areas worldwide. Psychotria spp. are mostly shrubs (a few being lianas, creepers or trees) and are often an important component of the undergrowth in tropical rainforests. Some show remarkable adaptations such as leaf bacterial symbiosis or litter gathering. Due to its size and identification problems, Psychotria remains a little-known genus, especially in West and Central Africa, where no major work has been done on this group since the 1960s.<p>The aims of the present work are: 1) a taxonomic revision of Psychotria in West and Central Africa; 2) a phylogenetic study of the genus, in order to trace its evolution and improve the infrageneric classification; and 3) a regional biogeographic study of the genus, to define centers of diversity and endemism.<p>Our taxonomical work, based on the study of herbarium specimens and field expeditions in Gabon and Cameroon, led us to recognise 232 species of Psychotria in West and Central Africa. Psychotria is therefore the largest plant genus in this area. Among these species, 78 are new.<p>Our phylogenetic work, based on two nuclear markers (ITS and ETS) and four chloroplastic markers (rps16, trnG, matK, rbcLa), shows that Petit’s (1964, 1966) infrageneric classification is in need of revision. In particular, we show that the two subgenera present in Africa (subg. Tetramerae and subg. Psychotria), which are defined by the presence or absence of leaf bacterial nodules, are not monophyletic: a secondary loss of the bacterial nodules has occured in some species. Our results also support the merging of the monospecific genus Peripeplus into Psychotria.<p>The genus Psychotria shows a remarkable diversity and a high level and endemism in the Lower Guinea domain (particularly Cameroon and Gabon) where several centers of endemism are identified. These are located not only in the inland hill ranges, which are well known for their particular flora, but also in littoral areas. West Africa is less diverse but also shows a high level of endemism, which concerns mostly two areas, one in Liberia and western Côte d’Ivoire and the other around the Côte d’Ivoire/Ghana border. The Congo basin, comparable in diversity to West Africa, has relatively few endemic species.<p>These results suggest that the rainforests of Cameroon and Gabon resisted relatively well during historical drier periods. They do not support the hypothesis of a disappearance of the Gulf of Guinea littoral forests during the Pleistocene.<p><p> / Doctorat en Sciences / info:eu-repo/semantics/nonPublished