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Houel, E., Gonzalez, G., Bessière, J. - M., Odonne, G., Eparvier, V., Deharo, E., et al. (2015). Therapeutic switching: From antidermatophytic essential oils to new leishmanicidal products. Memorias do Inst. Oswaldo Cruz, 110(1), 106–113.
Abstract: This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 μg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.
Keywords: Antifungal agents; Antiparasitic agents; Leishmania; Peritoneal macrophages – sesquiterpenes; Therapeutic switching
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Houel, E., Nardella, F., Jullian, V., Valentin, A., Vonthron-Sénécheau, C., Villa, P., et al. (2016). Wayanin and guaijaverin, two active metabolites found in a Psidium acutangulum Mart. ex DC (syn. P. persoonii McVaugh) (Myrtaceae) antimalarial decoction from the Wayana Amerindians. Journal of Ethnopharmacology, 187, 241–248.
Abstract: Ethnopharmacological relevance Psidium acutangulum Mart. ex DC is a small tree used by the Wayana Amerindians from the Upper-Maroni in French Guiana for the treatment of malaria. Aim of the study In a previous study, we highlighted the in vitro antiplasmodial, antioxidant and anti-inflammatory potential of the traditional decoction of P. acutangulum aerial parts. Our goal was then to investigate on the origin of the biological activity of the traditional remedy, and eventually characterize active constituents. Materials and methods Liquid-liquid extractions were performed on the decoction, and the antiplasmodial activity evaluated against chloroquine-resistant FcB1 ([3H]-hypoxanthine bioassay) and 7G8 (pLDH bioassay) P. falciparum strains, and on a chloroquine sensitive NF54 ([3H]-hypoxanthine bioassay) P. falciparum strain. The ethyl acetate fraction (D) was active and underwent bioguided fractionation. All the isolated compounds were tested on P. falciparum FcB1 strain. In vitro anti-inflammatory activity (IL-1β, IL-6, IL-8, TNFα) of the ethyl acetate fraction and of an anti-Plasmodium active compound, was concurrently assessed on LPS-stimulated human PBMC and NO secretion inhibition was measured on LPS stimulated RAW murine macrophages. Cytotoxicity of the fractions and pure compounds was measured on VERO cells, L6 mammalian cells, PBMCs, and RAW cells. Results Fractionation of the ethyl acetate soluble fraction (IC50 ranging from 3.4 to <1 μg/mL depending on the parasite strain) led to the isolation of six pure compounds: catechin and five glycosylated quercetin derivatives. These compounds have never been isolated from this plant species. Two of these compounds (wayanin and guaijaverin) were found to be moderately active against P. falciparum FcB1 in vitro (IC50 5.5 and 6.9 μM respectively). We proposed the name wayanin during public meetings organized in June 2015 in the Upper-Maroni villages, in homage to the medicinal knowledge of the Wayana population. At 50 μg/mL, the ethyl acetate fraction (D) significantly inhibited IL-1β secretion (-46%) and NO production (-21%), as previously observed for the decoction. The effects of D and guiajaverin (4) on the secretion of other cytokines or NO production were not significant. Conclusions The confirmed antiplasmodial activity of the ethyl acetate soluble fraction of the decoction and of the isolated compounds support the previous results obtained on the P. acutangulum decoction. The antiplasmodial activity might be due to a mixture of moderately active non-toxic flavonoids. The anti-inflammatory activities were less marked for ethyl acetate fraction (D) than for the decoction. © 2016 Elsevier Ireland Ltd. All rights reserved.
Keywords: Antimalarial; Cytokines; French guiana; Glycosylated flavonols; Psidium acutangulum; Traditional remedy
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Houel, E., Rodrigues, A. M. S., Jahn-Oyac, A., Bessière, J. - M., Eparvier, V., Deharo, E., et al. (2014). In vitro antidermatophytic activity of Otacanthus azureus (Linden) Ronse essential oil alone and in combination with azoles. J. Appl. Microbiol., 116(2), 288–294.
Abstract: Aims: We determined the chemical composition and investigated the antifungal activity of Otacanthus azureus (Linden) Ronse essential oil (EO) against a range of dermatophytes alone or in combination with azole antifungals. Methods and Results: Aerial parts of the plant were steam-distilled and the obtained oil was analysed by gas chromatography/mass spectrometry and 1H-NMR. It was shown to be largely composed of sesquiterpenes, with the main component being β-copaen-4-α-ol. Using broth microdilution techniques, this oil was found to have remarkable in vitro antifungal activities. Minimum inhibitory concentrations as low as 4 μg ml-1 were recorded. The analysis of the combined effect of the O. azureus EO with azoles using chequerboard assays revealed a synergism between the EO and ketoconazole, fluconazole or itraconazole against Trichophyton mentagrophytes. Notably, the O. azureus essential oil showed low cytotoxicity to VERO cells. Conclusions: The O. azureus essential oil alone or in combination with azoles is a promising antifungal agent in the treatment for human dermatomycoses caused by filamentous fungi. Significance and Impact of the Study: There is much interest in the study of essential oils for the discovery of new antimicrobial drugs. This study has highlighted the antidermatophytic activity of the O. azureus EO. © 2013 The Society for Applied Microbiology.
Keywords: Antifungal activity; Azoles; Dermatophytes; Essential oil; Otacanthus azureus; Synergy
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Odonne, G., Bourdy, G., Beauchene, J., Houel, E., Stien, D., Chevolot, L., et al. (2007). From Tonic-cups to Bitter-cups: Kwasi bita beker from Suriname Determination, past and present use of an ancient galenic artefact. J. Ethnopharmacol., 110(2), 318–322.
Abstract: In the main markets of Paramaribo (Suriname), many stands offer what is locally called “Bitter-cups”, or “Kwasi bita beker”, small footed-cups, roughly carved from a whitish wood. The use of these cups is strictly medicinal and it seems to be restricted to Suriname, as they are not found in neighbouring countries (Guyana, French Guiana). The aim of this study was to identify the botanical origin of Bitter-cups still in use in the Saramaka traditional medicine (as information from field people was controversial), and document the ethnopharmacology of this original galenical artefact. Microscopic and high performance liquid chromatography (HPLC) analyses were carried out on Bitter-cup, and anatomical criteria (marginal parenchyma band, size of intervessel and vessel-ray pits, rays width and rays composition, vessels clustering, frequency and size of parenchyma pits) together with HPLC profiles of the macerates showed that the wood cup was similar to Quassia amara L. (Simaroubaceae) wood. Ethnopharmacological investigation indicates that the use of these cups is simply due to the pharmacological properties attributed to “bitters”, and is strongly linked to tradition and cultural attitudes. This study also emphasizes the long lasting use of these cups, now restricted to Suriname only, with almost no variation over one century. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Tonic-cup; Bitter-cup; Quassia amara; Suriname; traditional remedy
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Odonne, G., Houel, E., Bourdy, G., & Stien, D. (2017). Treating leishmaniasis in Amazonia: A review of ethnomedicinal concepts and pharmaco-chemical analysis of traditional treatments to inspire modern phytotherapies. Journal of Ethnopharmacology, 199, 211–230.
Abstract: Ethnopharmacological relevance Cutaneous and mucocutaneous leishmaniasis are neglected tropical diseases that occur in all intertropical regions of the world. Amazonian populations have developed an abundant knowledge of the disease and its remedies. Therefore, we undertook to review traditional antileishmanial plants in Amazonia and have developed new tools to analyze this somewhat dispersed information. Material and methods A literature review of traditional remedies for cutaneous/mucocutaneous leishmaniasis in the Amazon was conducted and the data obtained was used to calculate distribution indexes designed to highlight the most relevant uses in Amazonia. The cultural distribution index represents the distribution rate of a given taxon among different cultural groups and was calculated as the ratio of the number of groups using the taxon to the total number of groups cited. The geographical distribution index allowed us to quantify spatial distribution of a taxon's uses in Amazonia and was calculated geometrically by measuring the average distance between the points where uses have been reported and the barycenter of those points. The general distribution index was defined as an arithmetic combination of the previous two and provides information on both cultural and spatial criteria. Results 475 use reports, concerning 291 botanical species belonging to 83 families have been gathered depicted from 29 sources. Uses concern 34 cultural groups. While the use of some taxa appears to be Pan-Amazonian, some others are clearly restricted to small geographical regions. Particular attention has been paid to the recipes and beliefs surrounding treatments. Topical application of the remedies dominated the other means of administration and this deserves particular attention as the main treatments against Neotropical leishmaniasis are painful systemic injections. The data set was analyzed using the previously defined distribution indexes and the most relevant taxa were further discussed from a phytochemical and pharmacological point of view. Conclusions The Amazonian biodiversity and cultural heritage host a fantastic amount of data whose systematic investigation should allow a better large-scale understanding of the dynamics of traditional therapies and the consequent discovery of therapeutic solutions for neglected diseases. Distribution indices are indeed powerful tools for emphasizing the most relevant treatments against a given disease and should be very useful in the meta-analysis of other regional pharmacopeia. This focus on renowned remedies that have not yet benefitted from extended laboratory studies, could stimulate future research on new treatments of natural origin for leishmaniasis. © 2017 Elsevier Ireland Ltd
Keywords: Amazonia; Distribution indexes; Ethnomedecine; Interculturality; Leishmaniasis; Medicinal plants; Traditional medicine
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