Tél. : (+594) 5 94 29 26 13
Fax : (+594) 5 94 28 47 86
email : Emeline.Houel at EcoFoG.gf
Position
Research Engineer at UMR EcoFoG.
Bioactive natural substances from the Amazonian flora
Natural products, either as pure compound or as standardized plant extracts, provide unlimited opportunities for new drug leads. This work will be divided in two parts: an activity-guided isolation of antiplasmodial molecules performed on two plants, Quassia amara L. and Psidium acutangulum DC., and the identification of new essential oils presenting antifungal activities against human dermatophytes and yeasts. These studies will be centered on the Guianese flora. French Guiana records high malaria incidence rates. The traditional antimalarial remedy most widespread and still very much in use there is a tea made out from Quassia amara mature leaves. The antimalarial activity of this preparation was previously assessed and in order to optimize the in vitro activity, different types of preparation have been realized and tested. The most active in vitro preparation is an infusion of fresh young leaves. Our next objective was to assess whether it could be contemplated to recommend this young leaves tea for treatment against malaria, since it seemed from literature precedent that SkD was also cytotoxic to a number of cellular lineages. A second phytotherapeutic remedy, localized to the Wayana community (Haut-Maroni) will also be submitted to bioguided fractionation to evaluate its antiplasmodial activity. Moreover, the incidence of fungal infections has been increasing in recent years due to a growing number of high-risk patients. This fact, coupled with the resistance to antibiotics and the toxicity during prolonged treatment with many antifungal drugs, has prompted an extensive search for newer drugs to treat mycosis. This search for biologically active substances has encouraged, among other things, the use of essential oils.The aim of this present study is to identify new essential oils presenting antifungal activities against human dermatophytes and yeasts and to determine their chemical composition.
Publications for EcoFoG
Houel, E., et al. "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 (2016): 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., et al. "Antiplasmodial and anti-inflammatory effects of an antimalarial remedy from the Wayana Amerindians, French Guiana: Takamalaimë (Psidium acutangulum Mart. ex DC., Myrtaceae)." Journal of Ethnopharmacology. 166 (2015): 279–285.
Abstract: Ethnopharmacological relevance:
Field investigations highlighted the use of Psidium acutangulum Mart. ex DC (syn. P. persoonii McVaugh), a small tree used by the Wayana Amerindians in Twenke–Taluhwen and Antecume–Pata, French Guiana, for the treatment of malaria, and administered either orally in the form of a decoction or applied externally over the whole body. This use appears limited to the Wayana cultural group in French Guiana and has never been reported anywhere else. Our goal was to evaluate the antimalarial and anti-inflammatory activities of a P. acutangulum decoction to explain the good reputation of this remedy.
Materials and methods:
Interviews with the Wayana inhabitants of Twenke–Taluhwen and Antecume–Pata were conducted within the TRAMAZ project according to the TRAMIL methodology, which is based on a quantitative and qualitative analysis of medicinal plant uses. A decoction of dried aerial parts of P. acutangulum was prepared in consistency with the Wayana recipe. In vitro antiplasmodial assays were performed on chloroquine-resistant FcB1 ([3H]-hypoxanthine bioassay) and 7G8 (pLDH bioassay) P. falciparum strains and on chloroquine sensitive NF54 ([3H]-hypoxanthine bioassay) P. falciparum strain. In vitro anti-inflammatory activity (IL-1β, IL-6, IL-8, TNFα) was evaluated on LPS-stimulated human PBMC and NO secretion inhibition was measured on LPS stimulated RAW murine macrophages. Cytotoxicity of the decoction was measured on L6 mammalian cells, PBMCs, and RAW cells. A preliminary evaluation of the in vivo antimalarial activity of the decoction, administered orally twice daily, was assessed by the classical four-day suppressive test against P. berghei NK65 in mice.
Results:
The decoction displayed a good antiplasmodial activity in vitro against the three tested strains, regardless to the bioassay used, with IC50 values of 3.3 µg/mL and 10.3 µg/mL against P. falciparum FcB1 and NF54, respectively and 19.0 µg/mL against P. falciparum 7G8. It also exhibited significant anti-inflammatory activity in vitro in a dose dependent manner. At a concentration of 50 µg/mL, the decoction inhibited the secretion of the following pro-inflammatory cytokines: TNFα (−18%), IL-1β (−58%), IL-6 (−32%), IL-8 (−21%). It also exhibited a mild NO secretion inhibition (−13%) at the same concentration. The decoction was non-cytotoxic against L6 cells (IC50>100 µg/mL), RAW cells and PBMC. In vivo, 150 µL of the decoction given orally twice a day (equivalent to 350 mg/kg/day of dried extract) inhibited 39.7% average parasite growth, with more than 50% of inhibition in three mice over five. The absence of response for the two remaining mice, however, induced a strong standard deviation.
Conclusions:
This study highlighted the in vitro antiplasmodial activity of the decoction of P. acutangulum aerial parts, used by Wayana Amerindians from the Upper-Maroni in French Guiana in case of malaria. Its antioxidant and anti-inflammatory potential, which may help to explain its use against this disease, was demonstrated using models of artificially stimulated cells.
Keywords: Psidium acutangulum; Plasmodium; Cytokines; Antimalarial; French Guiana; Traditional medicine
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Houel, E., et al. "Therapeutic switching: From antidermatophytic essential oils to new leishmanicidal products." Memorias do Inst. Oswaldo Cruz. 110.1 (2015): 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., et al. "In vitro antidermatophytic activity of Otacanthus azureus (Linden) Ronse essential oil alone and in combination with azoles." J. Appl. Microbiol.. 116.2 (2014): 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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Courtois, E. A., et al. "Differences in volatile terpene composition between the bark and leaves of tropical tree species." Phytochemistry. 82 (2012): 81–88.
Abstract: Volatile terpenes are among the most diverse class of defensive compounds in plants, and they are implicated in both direct and indirect defense against herbivores. In terpenes, both the quantity and the diversity of compounds appear to increase the efficiency of defense as a diverse blend of compounds provides a more efficient protection against a broader range of herbivores and limits the chances that an enemy evolves resistance. Theory predicts that plant defensive compounds should be allocated differentially among tissues according to the value of the tissue, its cost of construction and the herbivore pressure on it. We collected volatile terpenes from bark and leaves of 178 individual tree belonging to 55 angiosperm species in French Guiana and compare the kind, amount, and diversity of compounds in these tissues. We hypothesized that in woody plants, the outermost part of the trunk should hold a more diverse blend of volatile terpenes. Additionally, as herbivore communities associated with the leaves is different to the one associated with the bark, we also hypothesized that terpene blends should be distinct in the bark vs. the leaves of a given species. We found that the mixture of volatile terpenes released by bark is different and more diverse than that released by leaves, both in monoterpenes and sesquiterpenes. This supports our hypothesis and further suggests that the emission of terpenes by the bark should be more important for trunk defense than previously thought.
Keywords: French Guiana; Herbivory; Optimal defense theory; Secondary metabolites; Wood
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Emeline Houël