Allison Ledoux

Antiplasmodial activity of Mezoneuron benthamianum leaves and identification of its active constituents

ETHNOPHARMACOLOGICAL RELEVANCE Decoctions of the leaves of M. benthamianum Baill. are used by traditional healers in Guinea to treat malaria and this use was validated by a preliminary clinical assay. AIM OF THE STUDY To evaluate the in vitro antiplasmodial activity and to identify active compounds from extracts of M. benthamianum leaves. MATERIAL AND METHODS Antiplasmodial activity of extracts, fractions and pure compounds was evaluated in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) using the measurement of the plasmodial lactate dehydrogenase activity. Selectivity of extracts and purified compounds for Plasmodium parasites was evaluated by using WST-1 test on HeLa human cells. Compounds were isolated using normal phase silica gel column chromatography and prepHPLC and their structures elucidated using extensive spectroscopic analysis. RESULTS Hydroethanolic extracts (70% v/v) of M. benthamianum leaves showed a moderate in vitro activity against P. falciparum 3D7, with IC50 in the range 22.5 - 32.6µg/mL, depending on the batch; while a dark precipitate formed during ethanol evaporation showed higher activity (IC50 =6.5µg/mL). The fractionation was performed on this most active fraction and was followed by in vitro antiplasmodial assay. Active compounds (5, 7, 8) belong to several phytochemical classes, contributing together to the global antiplasmodial activity of the hydroethanolic extract against P. falciparum parasite. This study finally allowed the isolation of three diterpenes including two new compounds named Mezobenthamic acids A (1) and B (2) and neocaesalpin H (3), as well as quercetin (4), kaempferol (7), resveratrol (6), gallic acid (9) and its ethylester (5), β-sitosterol glucoside (10) and 13b-hydroxy-pheophorbide a (8). CONCLUSION This study gives some concrete evidence to support the ethnopharmacological use of Mezoneuron benthamianum leaves extract in the management of malaria. The active compounds can be further studied for their antiplasmodial potential, as well as their suitability to be used as quality markers for the standardization of this herbal drug from the Guinean traditional pharmacopeia.

In vivo Antimalarial and Antitrypanosomal Activity of Strychnogucine B, a Bisindole Alkaloid from Strychnos icaja

Strychnogucine B is a bisindole alkaloid previously isolated from Strychnos icaja that possesses promising in vitro antiplasmodial properties. This compound was synthesized in four steps from (-)-strychnine. As no acute toxicity was observed at the highest tested cumulative dose of 60 mg/kg, its in vivo antimalarial activity was determined intraperitoneally at 30 mg/kg/d in a Plasmodium berghei murine model. In the Peterss 4-d suppressive test, this alkaloid suppressed the parasitaemia by almost 36% on day 5 and 60% on day 7 compared to vehicle-treated mice. In addition to this interesting antimalarial activity, it showed moderate in vitro antitrypanosomal activity but no in vivo activity in an acute Trypanosoma brucei model. It was also inactive in vitro on Leishmania mexicana promastigotes. This highlights its selective antimalarial efficacy and leads to further investigation to assess its potential as new antimalarial lead compound.

In vitro antiplasmodial and cytotoxic activities of sesquiterpene lactones from Vernonia fimbrillifera Less. (Asteraceae)

Abstract Due to the in vitro antiplasmodial activity of leaf extracts from Vernonia fimbrillifera Less. (Asteraceae), a bioactivity-guided fractionation was carried out. Three sesquiterpene lactones were isolated, namely 8-(4’-hydroxymethacrylate)-dehydromelitensin (1), onopordopicrin (2) and 8α-[4’-hydroxymethacryloyloxy]-4-epi-sonchucarpolide (3). Their structures were elucidated by spectroscopic methods (1D and 2D NMR and MS analyses) and by comparison with published data. The isolated compounds exhibited antiplasmodial activity with IC50 values ≤ 5 μg/mL. Cytotoxicity of the compounds against a human cancer cell line (HeLa) and a mouse lung epithelial cell line (MLE12) was assessed to determine selectivity. Compound 3 displayed promising selective antiplasmodial activity (SI > 10).

Flavonoid composition, cellular antioxidant activity and (myelo)peroxidase inhibition of a Bryonia alba L. (Cucurbitaceae) leaves extract

The aim of the present study consisted in the isolation of flavonoids from the leaves of Bryonia alba L. and evaluation of their antioxidant activity and inhibition on peroxidase‐catalysed reactions.

Metabolomics analysis of Galium odoratum (L.) Scop.: impact of the plant population origin and growth conditions.

IntroductionGalium odoratum is a plant used in traditional medicine and to prepare beverages. Objective: To study the impact of plant origin and growth conditions on the metabolite content of the plant. Material and methods: Aerial biomass of Galium odoratum was collected from five natural populations (in situ conditions) and from controlled environment (ex situ conditions). NMR-based fingerprinting method was successfully applied to the discriminating chemical profiling of the in situ and ex situ samples. Results: Quantitative analysis of selected phytochemicals including phenylpropranoids and iridoids showed clear differences between the plants from nature and those of controlled growth conditions as well as internal variation within the group. The metabolomic approach emphasized the decrease of the secondary metabolites pool paralleled by an increase of the carbohydrates in ex situ conditions. The quantitative HPLC-UV points out slight variations of each of the analyzed secondary metabolites between populations in natural environment, variations maintained for three populations in the controlled conditions. Conclusion: Metabolomics approaches using H-NMR and HPLC are worth to consider for studying the impact of climate factors on the regulation of the phytochemical profile in relation to the origin of the plant material.