Historique de la colonisation du milieu de la presqu' île d'Ampasindava : transformations du paysage et système de conservation

In the northwest of Madagascar, the Ampasindava peninsula is home to the essential part of what  remains of the forests of the Sambirano phytogeographic domain. The area has great importance in terms of biogeography, ecology, and socio-cultural aspects. The first documented human presence dates back  to the tenth century, during the development of the maritime trade in Madagascar, before becoming the first headquarters of the Sakalava kingdom in the  northwest of Madagascar. Several facts contributed to the degradation of the landscape, like the practice of the tavy and the war between Bemihisatra and  Merina. In the peninsula, the western part was the most affected, on contrary to the eastern part where are located the forest massifs which served as refuges during the tribal wars. After the annexion by France, of an important territory including the peninsula (August 6th, 1896), the Merina left the region,  and these forest massifs acquired a sacred status and as such were protected against destruction, preserving the characteristics of the primary forests of Sambirano. Elsewhere, a process of natural  reconstruction of the vegetation started. These historic facts lead us to conclude that the forests of Dypsis spp. (Arecaceae) and Sarcolaenaceae are not primary resulting from a difference in substrate or  climate, but are to be interpreted as old secondary forests, deriving from the long-term process of  reconstruction of the vegetation. For several years, the analysis of satellite imagery demonstrates that the rhythm of the tavy has dramatically increased in the region. This increase stems not only from a population growth, but also from a growing pressure for land to generate income for the purchase of manufactured products. The practice of the tavy represents a major threat to forests and different types of residual natural habitats. Secondary forests are the most sensitive and most suitable for rice production. Primary sacred forests have remained so far untouched. Their traditional protection is however recently shaken by the influx of immigrants, who show little respect to traditional ban.  Dans le Nord-ouest de Madagascar, la presqu’île d’Ampasindava abrite une partie essentielle des restes  des forêts du domaine du Sambirano. La région possède une grande importance tant biogéographique et écologique, que socio-culturelle. Elle a connu au Xe siècle sa première implantation humaine et il est  vraisemblable que l’Homme l’ait parcourue et utilisée régulièrement à l’époque du développement du réseau maritime à Madagascar, avant que le Sambirano ne devienne le premier siège du royaume  Sakalava dans le Nord-ouest de l’île. Plusieurs faits ont contribué à la déstructuration du paysage écologique initial, comme la pratique de l’abattis sur brûlis ou tavy et les guerres entre les Bemihisatra de la région et l’armée du royaume Merina. Si la zone Ouest de la région a été la plus touchée, celle de l’Est où se trouvent les grands massifs forestiers a servi de refuges durant ces guerres. Après l’annexion par la France, le 6 août 1896, d’un important territoire comprenant la presqu’île, les Merina ont quitté la région, et ces massifs forestiers acquirent un caractère sacré et furent ainsi protégés contre la destruction et le défrichement en conservant les caractéristiques des forêts climaciques intactes du Sambirano. Ailleurs, un processus de reconstitution naturelle de la végétation se mit en route. Ces divers aspects historiques permettent d’avancer que les forêts à Sarcolaenaceae et à Dypsis spp (Arecaceae), avec leurs caractéristiques physionomiques, structurales et floristiques, ne découlent pas tant de  caractéristiques du substrat ou du climat, mais seraient plutôt des forêts secondaires âgées, issues du long processus d’évolution progressive du dynamisme de la succession végétale. Depuis  quelques  années, l’analyse des images satellite montre que le rythme auquel le tavy est pratiqué s’intensifie dans la région. Cet accroissement découle non seulement de la croissance démographique, mais aussi d’un  besoin accru en terres pour générer les revenus nécessaires à l’achat de produits manufacturés. La pratique du tavy représente une des principales menaces pour les forêts et les différents types d’habitats naturels résiduels. Les forêts secondaires âgées qui sont situées hors des zones traditionnellement protégées sont les plus sensibles car elles sont les plus propices à la production de riz. Les forêts des   massifs sacrés, en revanche, ne semblent pas encore réellement menacées mais leur protection  traditionnelle est quelque peu ébranlée depuis par l’arrivée récente et massive d’immigrants qui  respectent peu les interdits traditionnels

Chemical composition of Cinnamosma madagascariensis (Cannelaceae) essential oil and its larvicidal potential against the filariasis vector Culex quinquefasciatus Say

Madagascar flora is diverse and unique. Cinnamosma madagascariensis is an endemic species widely present in the forests of Madagascar. This plant has important traditional uses ranging from management of dementia, epilepsy, headache to malaria. Fewdata have been reported about the chemical composition of the essential oil, and no studies have been published on its bioactivity againstmosquitoes. Here,we focus on the chemical composition of essential oils extracted from C. madagascariensis stem bark and leaves, and their larvicidal potential against the filariasis vector Culex quinquefasciatus. GC-MS analysis revealed differences between the chemical volatile profiles of leaves and bark oils. In the former, linalool (30.1%), limonene (12.0%), myrcene (8.9%) and α-pinene (8.4%) were the major constituents, while in the latter β-pinene (33.3%), α-pinene (19.3%) and limonene (12.0%) were the most representative compounds. Acute toxicity experiments conducted on larvae of the filariasis vector C. quinquefasciatus led to LC50 of 61.6 μL L−1 and 80.1 μL L−1 for the bark and the leaf essential oils, respectively. Overall, the chance to use compounds from the C. madagascariensis bark and leaf essential oils against filariasis vectors seems promising, since they are effective at moderate doses and could be an advantageous alternative to build newer and safer mosquito control tools. To the best of our knowledge, this is the first report about the chemical composition of C. madagascariensis essential oils

Do ethnobotanical and laboratory data predict clinical safety and efficacy of anti-malarial plants?

<p>Abstract</p> <p>Background</p> <p>Over 1200 plant species are reported in ethnobotanical studies for the treatment of malaria and fevers, so it is important to prioritize plants for further development of anti-malarials.</p> <p>Methods</p> <p>The “RITAM score” was designed to combine information from systematic literature searches of published ethnobotanical studies and laboratory pharmacological studies of efficacy and safety, in order to prioritize plants for further research. It was evaluated by correlating it with the results of clinical trials.</p> <p>Results and discussion</p> <p>The laboratory efficacy score correlated with clinical parasite clearance (r_s=0.7). The ethnobotanical component correlated weakly with clinical symptom clearance but not with parasite clearance. The safety component was difficult to validate as all plants entering clinical trials were generally considered safe, so there was no clinical data on toxic plants.</p> <p>Conclusion</p> <p>The RITAM score (especially the efficacy and safety components) can be used as part of the selection process for prioritising plants for further research as anti-malarial drug candidates. The validation in this study was limited by the very small number of available clinical studies, and the heterogeneity of patients included.</p

Pre-hospital risk factors for inpatient death from severe febrile illness in Malian children.

BACKGROUND: Inpatient case fatality from severe malaria remains high in much of sub-Saharan Africa. The majority of these deaths occur within 24 hours of admission, suggesting that pre-hospital management may have an impact on the risk of case fatality. METHODS: Prospective cohort study, including questionnaire about pre-hospital treatment, of all 437 patients admitted with severe febrile illness (presumed to be severe malaria) to the paediatric ward in Sikasso Regional Hospital, Mali, in a two-month period. FINDINGS: The case fatality rate was 17.4%. Coma, hypoglycaemia and respiratory distress at admission were associated with significantly higher mortality. In multiple logistic regression models and in a survival analysis to examine pre-admission risk factors for case fatality, the only consistent and significant risk factor was sex. Girls were twice as likely to die as boys (AOR 2.00, 95% CI 1.08-3.70). There was a wide variety of pre-hospital treatments used, both modern and traditional. None had a consistent impact on the risk of death across different analyses. Reported use of traditional treatments was not associated with post-admission outcome. INTERPRETATION: Aside from well-recognised markers of severity, the main risk factor for death in this study was female sex, but this study cannot determine the reason why. Differences in pre-hospital treatments were not associated with case fatality

Plants used traditionally to treat malaria in Brazil: the archives of Flora Medicinal

The archives of Flora Medicinal, an ancient pharmaceutical laboratory that supported ethnomedical research in Brazil for more than 30 years, were searched for plants with antimalarial use. Forty plant species indicated to treat malaria were described by Dr. J. Monteiro da Silva (Flora Medicinal leader) and his co-workers. Eight species, Bathysa cuspidata, Cosmos sulphureus, Cecropia hololeuca, Erisma calcaratum, Gomphrena arborescens, Musa paradisiaca, Ocotea odorifera, and Pradosia lactescens, are related as antimalarial for the first time in ethnobotanical studies. Some species, including Mikania glomerata, Melampodium divaricatum, Galipea multiflora, Aspidosperma polyneuron, and Coutarea hexandra, were reported to have activity in malaria patients under clinical observation. In the information obtained, also, there were many details about the appropriate indication of each plant. For example, some plants are indicated to increase others' potency. There are also plants that are traditionally employed for specific symptoms or conditions that often accompany malaria, such as weakness, renal failure or cerebral malaria. Many plants that have been considered to lack activity against malaria due to absence of in vitro activity against Plasmodium can have other mechanisms of action. Thus researchers should observe ethnomedical information before deciding which kind of screening should be used in the search of antimalarial drugs

An update on the strategies in multicomponent activity monitoring within the phytopharmaceutical field

<p>Abstract</p> <p>Background</p> <p>To-date modern drug research has focused on the discovery and synthesis of single active substances. However, multicomponent preparations are gaining increasing importance in the phytopharmaceutical field by demonstrating beneficial properties with respect to efficacy and toxicity.</p> <p>Discussion</p> <p>In contrast to single drug combinations, a botanical multicomponent therapeutic possesses a complex repertoire of chemicals that belong to a variety of substance classes. This may explain the frequently observed pleiotropic bioactivity spectra of these compounds, which may also suggest that they possess novel therapeutic opportunities. Interestingly, considerable bioactivity properties are exhibited not only by remedies that contain high doses of phytochemicals with prominent pharmaceutical efficacy, but also preparations that lack a sole active principle component. Despite that each individual substance within these multicomponents has a low molar fraction, the therapeutic activity of these substances is established via a potentialization of their effects through combined and simultaneous attacks on multiple molecular targets. Although beneficial properties may emerge from such a broad range of perturbations on cellular machinery, validation and/or prediction of their activity profiles is accompanied with a variety of difficulties in generic risk-benefit assessments. Thus, it is recommended that a comprehensive strategy is implemented to cover the entirety of multicomponent-multitarget effects, so as to address the limitations of conventional approaches.</p> <p>Summary</p> <p>An integration of standard toxicological methods with selected pathway-focused bioassays and unbiased data acquisition strategies (such as gene expression analysis) would be advantageous in building an interaction network model to consider all of the effects, whether they were intended or adverse reactions.</p

Vasorelaxant activity of indole alkaloids from Tabernaemontana dichotoma.

The aim of this study was to search for bioactive natural products from medicinal plants targeting vasorelaxant activity and we found the methanol extract from bark of Tabernaemontana dichotoma showed vasorelaxant activity on rat aorta. We isolated eight indole alkaloids including 10-methoxyalstonerine (1), a new macroline type indole alkaloid, from bark of T. dichotoma. These were respectively identified as 10-methoxyaffinisine (2), lochnerine (3), cathafoline (4), (−)-alstonerine (5), 19,20-dehydro-10-methoxytalcarpine (6), alstonisine (7), and alstonal (8) based on spectroscopic analysis. Among them, sarpagine type (2 and 3), akuammiline type (4), and macroline oxindole type (7 and 8) showed potent vasorelaxant activity. Mechanism of action on vasorelaxant activity of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) was clarified. Effects of 10-methoxyaffinisine (2), cathafoline (4), and alstonisine (7) were partially mediated the NO release from endothelial cells. Furthermore, 10-methoxyaffinisine (2) and alstonisine (7) attribute to the inhibitory effect of VDC and ROC, and cathafoline (4) have inhibitory effect on Ca2+ influx via ROC. In addition, 10-methoxyaffinisine (2) as a major compound from bark of T. dichotoma showed hypotensive effect on normotensive rats in vivo

Functional Characterization of the Plasmodium falciparum Chloroquine-Resistance Transporter (PfCRT) in Transformed Dictyostelium discoideum Vesicles

Chloroquine (CQ)-resistant Plasmodium falciparum malaria has been a global health catastrophe, yet much about the CQ resistance (CQR) mechanism remains unclear. Hallmarks of the CQR phenotype include reduced accumulation of protonated CQ as a weak base in the digestive vacuole of the erythrocyte-stage parasite, and chemosensitization of CQ-resistant (but not CQ-sensitive) P. falciparum by agents such as verapamil. Mutations in the P. falciparum CQR transporter (PfCRT) confer CQR; particularly important among these mutations is the charge-loss substitution K→T at position 76. Dictyostelium discoideum transformed with mutant PfCRT expresses key features of CQR including reduced drug accumulation and verapamil chemosensitization.We describe the isolation and characterization of PfCRT-transformed, hematin-free vesicles from D. discoideum cells. These vesicles permit assessments of drug accumulation, pH, and membrane potential that are difficult or impossible with hematin-containing digestive vacuoles from P. falciparum-infected erythrocytes. Mutant PfCRT-transformed D. discoideum vesicles show features of the CQR phenotype, and manipulations of vesicle membrane potential by agents including ionophores produce large changes of CQ accumulation that are dissociated from vesicular pH. PfCRT in its native or mutant form blunts the ability of valinomycin to reduce CQ accumulation in transformed vesicles and decreases the ability of K(+) to reverse membrane potential hyperpolarization caused by valinomycin treatment.Isolated vesicles from mutant-PfCRT-transformed D. discoideum exhibit features of the CQR phenotype, consistent with evidence that the drug resistance mechanism operates at the P. falciparum digestive vacuole membrane in malaria. Membrane potential apart from pH has a major effect on the PfCRT-mediated CQR phenotype of D. discoideum vesicles. These results support a model of PfCRT as an electrochemical potential-driven transporter in the drug/metabolite superfamily that (appropriately mutated) acts as a saturable simple carrier for the facilitated diffusion of protonated CQ