In vitro Antileishmanial, Antitrypanosomal, and Anti-inflammatory-like Activity of Terminalia mollis Root Bark.

This study aims at determining the in vitro antitrypanosomal, antileishmanial, antioxidant, and anti-inflammatory-like activities of Terminalia mollis root crude extracts. The antitrypanosomal and antileishmanial activities on Trypanosoma brucei brucei (strain 427) and promastigotes of Leishmania mexicana mexicana (MHOM/BZ/84/BEL46) were evaluated in vitro. The methanolic root bark extract and standards were profiled by HPLC-PDA, and the majority of compounds identified using literature data. The in vitro antioxidant and anti-inflammatory-like activities were determined by evaluating the effect of crude extracts on reactive oxygen species produced by phorbol 12-myristate 13-acetate-stimulated equine neutrophils using lucigenin-enhanced chemiluminescence and on purified equine myeloperoxidase activity measured by specific immunological extraction followed by enzymatic detection. The methanolic, aqueous crude extract, and aqueous crude extract free of tannins exhibited good growth inhibition on Trypanosoma brucei brucei (IC50 3.72, 6.05, and 4.45 µg/mL respectively) but were inactive against Leishmania mexicana mexicana (IC50 > 100 µg/mL). Suramin (IC50 0.11 µg/mL) and amphotericin (IC50 0.11 µg/mL) were used as standard respectively for the antitrypanosomal and antileishmanial activity. Very interesting antioxidant and anti-inflammatory-like activities were observed with 50% hydroethanolic, aqueous crude extracts, and aqueous crude extract free of tannins as well as with pure punicalagin, gallic, and ellagic acid (IC50 0.38 - 10.51 µg/mL for 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), chemiluminescence, and specific immunological extraction followed by enzymatic detection assays. The study results support traditional medicinal use of the plant for the treatment of parasitical disorders and revealed for the first time the antitrypanosomal potential, anti-inflammatory-like, and antioxidant activity of Terminalia mollis root.

Strychnobaillonine, an unsymmetrical bisindole alkaloid with an unprecedented skeleton from Strychnos icaja roots.

A reinvestigation of the roots of Strychnos icaja resulted in the isolation of a new bisindole alkaloid named strychnobaillonine (1) with original C-17-N-1' and C-23-C-17' junctions, in addition to sungucine, bisnordihydrotoxiferine, and strychnohexamine (2). Compound 1 showed potent activity against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum in vitro with an IC50 value of 1.1 µM. The structures of the compounds were defined by detailed spectroscopic analyses, especially 1H and 13C NMR, DEPT, HSQC, COSY, NOESY, HMBC, and HRESIMS. The proposed absolute configuration was based on biosynthetic considerations and spectroscopic data (CD, NMR) supported by molecular modeling.

In vitro and in vivo antiplasmodial activity of three Rwandan medicinal plants and identification of their active compounds.

In our previous study, we reported the interesting in vitro antiplasmodial activity of some Rwandan plant extracts. This gave rise to the need for these extracts to also be evaluated in vivo and to identify the compounds responsible for their antiplasmodial activity. The aim of our study was, on the one hand, to evaluate the antiplasmodial activity in vivo and the safety of the selected Rwandan medicinal plants used in the treatment of malaria, with the objective of promoting the development of improved traditional medicines and, on the other hand, to identify the active ingredients in the plants. Plant extracts were selected according to their selectivity index. The in vivo antiplasmodial activity of aqueous, methanolic, and dichloromethane extracts was then evaluated using the classical 4-day suppressive test on Plasmodium berghei infected mice. The activity of the plant extracts was estimated by measuring the percentage of parasitemia reduction, and the survival of the experimental animals was recorded. A bioguided fractionation was performed for the most promising plants, in terms of antiplasmodial activity, in order to isolate active compounds identified by means of spectroscopic and spectrometric methods. The highest level of antiplasmodial activity was observed with the methanolic extract of Fuerstia africana (> 70 %) on days 4 and 7 post-treatment after intraperitoneal injection and on day 7 using oral administration. After oral administration, the level of parasitemia reduction observed on day 4 post-infection was 44 % and 37 % with the aqueous extract of Terminalia mollis and Zanthoxylum chalybeum, respectively. However, the Z. chalybeum extract presented a high level of toxicity after intraperitoneal injection, with no animals surviving on day 1 post-treatment. F. africana, on the other hand, was safer with 40 % mouse survival on day 20 post-treatment. Ferruginol is already known as the active ingredient in F. Africana, and ellagic acid (IC50 = 175 ng/mL) and nitidine (IC50 = 77.5 ng/mL) were identified as the main active constituents of T. mollis and Z. chalybeum, respectively. F. africana presented very promising antiplasmodial activity in vivo. Although most of the plants tested showed some level of antiplasmodial activity, some of these plants may be toxic. This study revealed for the first time the role of ellagic acid and nitidine as the main antimalarial compounds in T. mollis and Z. chalybeum, respectively.

Unusual amino acids and monofluoroacetate from Dichapetalum michelsonii (Umutambasha), a toxic plant from Rwanda.

In the course of our investigations on Umutambasha in order to identify its convulsant principles, small quantities of monofluoroacetate were observed in stem bark, leaves, and fruits of this plant newly identified as Dichapetalum michelsonii Hauman. Conclusive evidence for a monofluoroacetate presence came from its isolation from the freeze-dried extract of stem bark. Three free unusual amino acids, named N-methyl-α-alanine, N-methyl-ß-alanine, and 2,7-diaminooctan-1,8-dioic acid, described for the first time in a plant, and known trigonelline were also isolated from the stem bark of D. michelsonii. Structure elucidations were mainly achieved by spectroscopic methods (1H-NMR, 2D-NMR, MS) and by comparison with authentic references. These unusual amino acids were detected by a fast, reliable TLC analysis in all our batches of Umutambasha, suggesting that they could be used for identification purposes in case of human or livestock intoxications. Finally, EEG recordings and behavioural observations performed in mice suggested that the convulsive patterns produced by Umutambasha are the consequence of monofluoroacetate presence in D. michelsonii.

Isolation, pharmacological activity and structure determination of physalin B and 5ß,6ß-epoxyphysalin B isolated from Congolese Physalis angulata L.

Physalis angulata L., an annual herb from the Solanaceae family, is widely used in popular medicine in tropical countries to treat a variety of diseases. Two products, (X) and (Y), were isolated from a crude CH2Cl2 extract of dried Congolese Physalis angulata L. plants and crystallized from acetone for structure elucidation. Compound (X) corresponds to a physalin B dimer acetone solvate hydrate (2C28H30O9·C3H6O·0.22H2O), while compound (Y) crystallizes as a mixed crystal containing two physalin B molecules which overlap with 5ß,6ß-epoxyphysalin B, also known as physalin F, and one acetone molecule in the asymmetric unit (1.332C28H30O9·0.668C28H30O10·C3H6O). Antiplasmodial activity, cytotoxic activity and selectivity indices were determined for crude extracts and the two isolated products (X) and (Y).

Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound.

BACKGROUND: Natural products could play an important role in the challenge to discover new anti-malarial drugs. In a previous study, Dicoma tomentosa (Asteraceae) was selected for its promising anti-plasmodial activity after a preliminary screening of several plants traditionally used in Burkina Faso to treat malaria. The aim of the present study was to further investigate the anti-plasmodial properties of this plant and to isolate the active anti-plasmodial compounds. METHODS: Eight crude extracts obtained from D. tomentosa whole plant were tested in vitro against two Plasmodium falciparum strains (3D7 and W2) using the p-LDH assay (colorimetric method). The Peters' four-days suppressive test model (Plasmodium berghei-infected mice) was used to evaluate the in vivo anti-plasmodial activity. An in vitro bioguided fractionation was undertaken on a dichloromethane extract, using preparative HPLC and TLC techniques. The identity of the pure compound was assessed using UV, MS and NMR spectroscopic analysis. In vitro cytotoxicity against WI38 human fibroblasts (WST-1 assay) and haemolytic activity were also evaluated for extracts and pure compounds in order to check selectivity. RESULTS: The best in vitro anti-plasmodial results were obtained with the dichloromethane, diethylether, ethylacetate and methanol extracts, which exhibited a high activity (IC50 ≤ 5 µg/ml). Hot water and hydroethanolic extracts also showed a good activity (IC50 ≤ 15 µg/ml), which confirmed the traditional use and the promising anti-malarial potential of the plant. The activity was also confirmed in vivo for all tested extracts. However, most of the active extracts also exhibited cytotoxic activity, but no extract was found to display any haemolytic activity. The bioguided fractionation process allowed to isolate and identify a sesquiterpene lactone (urospermal A-15-O-acetate) as the major anti-plasmodial compound of the plant (IC50 < 1 µg/ml against both 3D7 and W2 strains). This was also found to be the main cytotoxic compound (SI = 3.3). While this melampolide has already been described in the plant, this paper is the first report on the biological properties of this compound. CONCLUSIONS: The present study highlighted the very promising anti-plasmodial activity of D. tomentosa and enabled to identify its main active compound, urospermal A-15-O-acetate. The high anti-plasmodial activity of this compound merits further study about its anti-plasmodial mechanism of action. The active extracts of D. tomentosa, as well as urospermal A 15-O-acetate, displayed only a moderate selectivity, and further studies are needed to assess the safety of the use of the plant by the local population.

Antiplasmodial alkaloids from the stem bark of Strychnos malacoclados.

From the stem bark of Strychnos malacoclados, one new bisindole alkaloid, 3-hydroxylongicaudatine Y (1), was isolated along with the known alkaloids vomicine (2), bisnordihydrotoxiferine (3), divarine (4), longicaudatine (5), longicaudatine Y (6), and longicaudatine F (7). All the compounds were tested for their antimalarial activity against the chloroquine-sensitive 3D7 and -resistant W2 strains of Plasmodium falciparum. Longicaudatine was the most active compound with IC50 values of 0.682 and 0.573 µM, respectively. The activity of compounds 1, 3, 4, 6, and 7 against the two strains ranged from 1.191 to 6.220 µM and 0.573 to 21.848 µM, respectively. Vomicine (2), the only monomer isolated, was inactive. The alkaloids of the longicaudatine-type ( 1, 5-7) were more active than those of the caracurine-type (3- 4). The presence of the ether bridge in the molecule seems to increase the antiplasmodial activity. Compounds 1, 5, and 7 were tested against the WI-38 human fibroblast cell line. Longicaudatine was the most cytotoxic compound with an IC50 of 2.721 µM. Longicaudatine F was 40-46 times more active against the two strains of P. falciparum than against the human fibroblasts and was thus considered as the more selective alkaloid. The structures of the compounds were determined based on the analysis of their spectral data.

Polyphenol content and modulatory activities of some tropical dietary plant extracts on the oxidant activities of neutrophils and myeloperoxidase.

Young leaves of Manihot esculenta Crantz (Euphorbiaceae), Abelmoschus esculentus (Malvaceae), Hibiscus acetosella (Malvaceae) and Pteridium aquilinum (Dennstaedtiaceae) are currently consumed as green vegetables by peoples in sub-Saharan Africa, Latin America, Asia and their migrants living in Western Europe. Sub-Saharan peoples use Manihot, Abelmoschus and Hibiscus also in the folk medicine to alleviate fever and pain, in the treatment of conjunctivitis, rheumatism, hemorrhoid, abscesses, ... The present study investigates the effects of aqueous extracts of those plants on the production of reactive oxygen species (ROS) and the release of myeloperoxidase (MPO) by equine neutrophils activated with phorbol 12-myristate 13-acetate (PMA). The ROS production was measured by lucigenin-enhanced chemiluminescence (CL), and the release of total MPO by an ELISA method. The study also investigates the effect of the extracts on the activity of MPO by studying its nitration activity on tyrosine and by using a new technique called SIEFED (Specific Immunological Extraction Followed by Enzymatic Detection) that allows studying the direct interaction of compounds with the enzyme. In all experiments, the aqueous extracts of the plants developed concentration-dependent inhibitory effects. A moderate heat treatment did not significantly modify the inhibitory capacity of the extracts in comparison to not heated ones. Total polyphenol and flavonoid contents were determined with an HPLC-UV/DAD analysis and a spectroscopic method using Folin-Ciocalteu reagent. Some polyphenols with well-known antioxidant activities (caffeic acid, chlorogenic acid, hyperoside, rosmarinic acid and rutin) were found in the extracts and may partly explain the inhibitory activities observed. The role of those dietary and medicinal plants in the treatment of ROS-dependent inflammatory diseases could have new considerations for health.

Unveiling antiplasmodial alkaloids from a cumulative collection of Strychnos extracts by multi-informative molecular networks.

Malaria, a disease known for thousands of years and caused by parasites of the Plasmodium genus, continues to cause many deaths throughout the world today, particularly due to the emergence of parasite resistance to the current therapeutic arsenal. Plants of the Strychnos genus, remarkable due to their multiple traditional uses as well as their alkaloid content, are promising candidates to develop new antimalarial treatments. Indeed, previous research on this plant group has shown promising (≤ 5 µg/ml) or good (between 5 and 15 µg/ml) antiplasmodial activities. Using the chloroquine-sensitive strain of Plasmodium falciparum (3D7), and artemisinin as positive control, a screening of antiplasmodial activities from 43 crude methanolic extracts from 28 species of the Strychnos genus was carried out in three independent assays. A total of 12 extracts had good (6 extracts) or promising (6 extracts) antiplasmodial activities. These results allowed both to confirm known activities but also to detect new ones. These extracts were then analyzed by HPLC-ESI(+)-Q/TOF, and the processed MS/MS data allowed to generate a molecular network in which the antiplasmodial activities were implemented as metadata. The exploration of the molecular network revealed the presence of alkaloids still unknown, and potentially active against malaria, in particular alkaloids close to usambarensine and its derivatives. This study shows that the emergence of molecular networking offers new leads for identifications of alkaloids from the Strychnos genus. The presence of unknown alkaloids potentially active against malaria confirms all the interest to continue in studying the Strychnos genus. Bioassay- and mass-guided fractionations as well as various dereplication tools would allow to identify and characterize these interesting alkaloids further.

Biological Activities of Some Isoquinoline Alkaloids from Fumaria schleicheri Soy. Will.

Fumaria schleicheri Soy. Will. is a species belonging to the Papaveraceae family, being widespread in East-Central and Southern Europe. As with numerous other species of the genus, it is used in traditional medicine for the treatment of hepatobiliary and digestive disorders. The aim of the present study consisted of the evaluation of its alkaloid content and the assessment of its in vitro antioxidant, anti-cholinesterase and cytotoxic potential. Total alkaloid content in the composition of the species was quantified by a spectrophotometrical method and they were individually identified and quantified by HPLC-DAD. The antioxidant capacity was investigated by the DPPH and FRAP methods, while the anti-cholinesterase activity was assessed by an adapted Ellman's method. The in vitro cytotoxic activity was evaluated on BJ human fibroblasts and DLD-1 human colon adenocarcinoma cell lines. Results showed the presence of bicuculline, protopine, chelidonine, stylopine and sanguinarine, among which bicuculline, protopine, stylopine and sanguinarine were quantified, while the antioxidant and anti-cholinesterase assays showed valuable potentials. No cytotoxic effect was observed on BJ cell lines and selective cytotoxicity was expressed towards tumoral cells. In this context, F. schleicheri appears as an important medicinal species with significant potential of substitution with the officinal species.

Exploration by molecular networking of Strychnos alkaloids reveals the unexpected occurrence of strychnine in seven Strychnos species.

INTRODUCTION: Plants of the Strychnos genus, which include about 200 species, are used for multiple traditional purposes as hunting poison, for example, and have shown interesting pharmacological properties, especially curarizing and tetanizing, but also against malaria. Many monoterpene indole alkaloids have already been isolated and identified. Among them, there is strychnine, a famous alkaloid that can cause death by asphyxiation. OBJECTIVE: Investigate alkaloidic molecular diversity from Strychnos genus using molecular networking technique and study the Strychnos genus from a chemotaxonomic point of view. MATERIAL AND METHODS: Twenty-eight different species and different plant parts were ground into powder using a grinder. The methanolic extracts were carried out using a pressurized solvent extraction and the alkaloid extract was performed manually with a separating funnel. The extracts were analyzed by HPLC-ESI(+)-Q/TOF. The data were processed using MZmine 2 software and the molecular network was generated on the GNPS platform. The study of the generated molecular network allowed the detection of various alkaloids. Among these is the famous strychnine which has been detected in 7 new Strychnos species not yet described as strychnine producers. This identification was investigated using orthogonal approaches, namely TLC, NMR, HPLC-UV and UHPLC-ESI(+)-Q/TOF analyses. The LOD by HPLC-UV of strychnine was also determined. RESULTS: Further analyses allowed to confirm the presence of strychnine in S. densiflora trunk barks but also to show the presence of strychnine with high probability in the trunk barks of S. camptoneura, S. congolana, S. boonei, and S. tchibangensis, and in the leaves of S. usambarensis. About the trunk barks of S. tricalyisoides, the probability of a strychnine content remains low. CONCLUSION: This work exemplified the efficiency of molecular networking in identifying known metabolites (major and minor alkaloids) involved in the chemotaxonomic study of plants from Strychnos genus.

17-O-acetyl,10-hydroxycorynantheol, a selective antiplasmodial alkaloid isolated from Strychnos usambarensis leaves.

In the course of our investigations on Strychnos usambarensis leaves in order to isolate isostrychnopentamine, the main alkaloid responsible for the antiplasmodial activity of the plant, a new tertiary indolic alkaloid has been isolated: 17-O-acetyl,10-hydroxycorynantheol 1. Its structure was determined by means of spectroscopic and spectrometric methods such as UV, IR, CD, NMR, and ESI-MS. 17-O-acetyl,10-hydroxycorynantheol 1 is one of the most active monomeric indole alkaloids known to date showing an in vitro activity against Plasmodium falciparum close to 5 µM and a high selectivity.

Quality assessment of Polygonum cuspidatum and Polygonum multiflorum by 1H NMR metabolite fingerprinting and profiling analysis.

The quality assessment and control of traditional Chinese medicines (TCM) nowadays receives a great deal of attention worldwide and particularly in Europe with its increasing local use. Polygonum cuspidatum Siebold & Zucc. and Polygonum multiflorum Thunb. are two members of the Polygonaceae family, which are widely used as Chinese medicinal plants. The aim of this study was to achieve an overview of the quality of P. cuspidatum and P. multiflorum samples available on the Chinese market and to identify important metabolites for their discrimination, using (1)H NMR-based metabolomics. (1)H NMR and multivariate analysis techniques were applied to almost 60 plant samples collected in different places in China. Using (1)H NMR metabolomics, it was possible, without previous evaporation or separation steps, to obtain metabolic fingerprints to distinguish between the species. The important metabolites for discrimination were stilbene derivatives. Finally, a clear distinction between the two species was possible and the discriminant metabolites were identified.

Evaluation of the antioxidant activity of passion fruit (Passiflora edulis and Passiflora alata) extracts on stimulated neutrophils and myeloperoxidase activity assays.

The antioxidant activity of methanol extracts from Passiflora edulis and Passiflora alata pulp, and P. edulis rinds, healthy or infected with the passion fruit woodiness virus (PWV), was investigated using the oxidant activities of the neutrophil and the neutrophil granule enzyme myeloperoxidase (MPO), both playing key roles in inflammation. The reactive oxygen species produced by stimulated neutrophils were evaluated by lucigenin-enhanced chemiluminescence (CL) and the activity of purified MPO was measured by SIEFED (Specific Immunological Extraction Followed by Enzymatic Detection), a technique for studying the direct interaction of a compound with the enzyme. The rind extracts of P. edulis possessed higher and dose-dependent inhibitory effects on CL response and on the peroxidase activity of MPO than total pulp extracts from both passion fruit species. The quantification of isoorientin in the extracts showed a correlation with their antioxidant activity, suggesting the potential of P. edulis rinds as functional food or as a possible source of natural flavonoids.

Metabolomic analysis of Echinacea spp. by 1H nuclear magnetic resonance spectrometry and multivariate data analysis technique.

INTRODUCTION: The genus Echinacea (Asteraceae) comprises about 10 species originally distributed in North America. Three species are very well known as they are used worldwide as medicinal plants: Echinacea purpurea, E. pallida, E. angustifolia. OBJECTIVE: To discriminate between these three Echinacea species and E. simulata by (1)H NMR-based metabolomics. METHODOLOGY: (1)H NMR and multivariate analysis techniques were applied to diverse Echinacea plants including roots and aerial parts, authentic plants, commercial plants and commercial dry extracts. RESULTS: Using the (1)H NMR metabolomics, it was possible, without previous evaporation or separation steps, to obtain a metabolic fingerprint to distinguish between species. CONCLUSION: A clear distinction between the three pharmaceutical species was possible and some useful metabolites were identified.

In vitro anticancer potential of tree extracts from the Walloon Region forest.

Forty-eight extracts from 16 common Belgian trees from the Walloon Region forest were evaluated for in vitro growth inhibitory activity against the human LoVo colon cancer, PC3 prostate cancer, and U373 glioblastoma cell lines. Our study was performed with the aim of selecting plant candidates in order to later isolate new anticancer compounds from an easily affordable tree material. Extracts from Alnus glutinosa (stem bark), Carpinus betulus (leaves and stem bark), Castanea sativa (stem bark), Fagus sylvatica (leaves), Ilex aquifolium (leaves), Larix decidua (leaves), Quercus petraea (stem bark), and Quercus robur (leaves) showed for the first time potent in vitro growth inhibitory activity and could become easily affordable sources of potential new anticancer agents. Root extracts from Robinia pseudoacacia, already known for containing cytotoxic lectins, also showed interesting activity.

Flavonoid Analysis and Antioxidant Activities of the Bryonia alba L. Aerial Parts.

Bryonia alba L. is the only Bryonia species found in Romanian flora, being known as a remedy for inflammatory pathologies or for its hepatoprotective and adaptogen activities. The present investigation studied the flavonoid composition and antioxidant activities of the aerial parts of this species. Flavonoid profile was evaluated by HPLC coupled with Diode Array Detection (DAD), while antioxidant capacity was assessed by various methods, testing different antioxidant mechanisms: DPPH (2,2-diphenyl-1-picrylhydrazyl), CUPRAC (cupric reducing antioxidant capacity), FRAP (ferric reducing ability of plasma), TEAC (Trolox equivalent antioxidant capacity), EPR (electron paramagnetic resonance method) and SNPAC (silver nanoparticles antioxidant capacity). Cytotoxicity was tested on human cancerous and healthy cell lines. Anti-plasmodial tests were performed on two strains of Plasmodium falciparum. Whole organism toxicity was assessed on zebrafish larvae. The HPLC-DAD analysis proved the presence of lutonarin, saponarin, isoorientin, and isovitexin as the major flavonoids in the composition of tested samples. Significant results were obtained for all antioxidant capacity assays. The cytotoxicity tests proved the absence of cellular and parasitic toxicity and these results were confirmed by the lack of toxicity on the zebrafish larvae model. This study proves a promising potential of the aerial parts of Bryonia alba L. as antioxidant agents.

Chenopodium ambrosioides induces an endothelium-dependent relaxation of rat isolated aorta.

OBJECTIVE: This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioides on the isolated rat aorta, and to explore its mechanism of action. METHODS: The vasorelaxant effect and the mode of action of various extracts from the leaves of C. ambrosioides were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, ethyl acetate and methanol fractions were analyzed, using thin-layer chromatography and high-performance liquid chromatography techniques, for their polyphenolic content. RESULTS: The various active extracts of C. ambrosioides at four concentrations (10-3, 10-2, 10-1 and 1 mg/mL) relaxed the contraction elicited by phenylephrine, in a concentration-dependent manner. This effect seems to be endothelium-dependent, since the vasodilatory effect was entirely absent in denuded aortic rings. The vasorelaxant effect of the methanol fraction (MF) of C. ambrosioides at 1 mg/mL was also inhibited by atropine and tetraethylammonium. This effect remained unchanged by Nω-nitro-l-arginine methyl ester hydrochloride and glibenclamide. The preliminary phytochemical analysis showed that the leaves of C. ambrosioides are rich in phenolic and flavonoid derivatives. CONCLUSION: These results suggest that the MF of C. ambrosioides produces an endothelium-dependent relaxation of the isolated rat aorta, which is thought to be mediated mainly through stimulation of the muscarinic receptors, and probably involving the opening of Ca2+-activated potassium channels.

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

OBJECTIVES: 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. METHODS: Flavonoids were isolated by preparative HPLC-DAD and their structures were elucidated by MS and NMR. Inhibitory effect was tested by the horseradish peroxidase and the myeloperoxidase assays. Cellular antioxidant assays consisted in testing the inhibitory activity on the reactive oxygen species released upon activation of neutrophils freshly isolated ex vivo from equine blood and of human monocytes-derived macrophages in vitro. Whole organism toxicity was assessed on zebrafish larvae. KEY FINDINGS: Four flavonoids (lutonarin, saponarin, isoorientin and isovitexin) were isolated. The performed assays showed significant antioxidant activity and inhibition for the peroxidase-catalysed reactions. Absence of cellular and zebrafish toxicity was confirmed. CONCLUSIONS: Bryonia alba L. leaves are particularly interesting for their flavonoids content and showed significant inhibitory effect on peroxidase-catalysed oxidation of substrates (Amplex Red and L012), as well as antioxidant/antiradical activity, proving that this species has a medicinal potential. Moreover, the present study highlights the absence of the toxicity of these leaves and offers though a novel perspective on the species, previously known as being toxic.

Potential antimalarial activity of indole alkaloids.

New antimalarial treatments are now urgently required, following the emergence of resistance to the most used drugs. Natural products contribute greatly to the therapeutic arsenal in this area, including artemisinin and quinine (and atovaquone, semi-synthetic). Among the natural products, indole alkaloids represent an interesting class of compounds. Screening carried out to date has revealed several substances active in vitro under the micromolar range and with a good selectivity index. This review covers the indole alkaloids with high antiplasmodial activity (in vitro and in vivo) isolated from natural sources, and is organized according to the different chemical structures of the alkaloids.