Evelyne Ollivier

Ethnobotanical survey and in vitro antiplasmodial activity of plants used in traditional medicine in Burkina Faso

In Burkina Faso, most people in particular, in rural areas, use traditional medicine and medicinal plants to treat usual diseases. In the course of new antimalarial compounds, an ethnobotanical survey has been conducted in different regions. Seven plants, often cited by traditional practitioners and not chemically investigated, have been selected for an antiplasmodial screening: Pavetta crassipes (K. Schum), Acanthospermum hispidum (DC), Terminalia macroptera (Guill. et Perr), Cassia siamea (Lam), Ficus sycomorus (L), Fadogia agrestis (Schweinf. Ex Hiern) and Crossopteryx febrifuga (AFZ. Ex G. Don) Benth. Basic, chloroform, methanol, water-methanol and aqueous crude extracts have been prepared and tested on Plasmodium falciparum chloroquine-resistant W2 strain. A significant activity has been observed with alkaloid extract of P. crassipes (IC(50)<4 microg/ml), of A. hispidum, C. febrifuga, and F. agrestis (4<IC(50)<10 microg/ml). The best result is obtained with aqueous extract of T. macroptera with an IC(50)=1 microg/ml. These results confirm the traditional use of these plants.

Antimalarial activity of four plants used in traditional medicine in Mali

Mitragyna inermis (De Willd.) O. Kuntze Rubiaceae, Nauclea latifolia (Sm.) Rubiaceae, Glinus oppositofolius (Linn) Molluginaceae and Trichilia roka (Forsk.) Chiv. Meliaceae were investigated for their in vitro antimalarial activity. Leaves, roots and stem barks were submitted to aqueous, hydromethano and chloroform extractions and antimalarial activity was evaluated by microscopic and flow cytometric analysis. The results present evidence that the alkaloids contained in chloroform extracts and ursolic acid, purified from the hydromethanol extract of M. inermis induced a significant decrease of parasite proliferation. However, aqueous extracts, traditionally used for medication did not show high antimalarial activity. Statistical comparison between microscopic and cytometric analysis demonstrated the validity of this new technique for the screening of active antimalarial compounds isolated from plants. Copyright

Antiplasmodial, anti-inflammatory and cytotoxic activities of various plant extracts from the Mascarene Archipelago.

AIM OF THE STUDY Antiplasmodial activity, inhibition of nitric oxide (NO) overproduction, and anti-proliferative activity were investigated in vitro to evaluate the bioactive potential of the traditional pharmacopoeia of the Mascarene Archipelago, which is known for its biodiversity and for the richness of its endemic flora. MATERIALS AND METHODS A total of 45 methanol (MeOH) and dichloromethane (DCM) extracts were prepared from 19 plant species collected on Réunion and Mauritius Islands. Ninety-six-well microplate assays were performed on chloroquine sensitive Plasmodium falciparum 3D7 strain, on LPS-stimulated Raw 264.7 murine macrophages and on A-549, DLD-1 and WS1 human cells. Activity was evaluated through spectrophotometric methods. RESULTS Activity was attributed to plant extracts expressing IC(50)<50μg/ml for antiplasmodial response, IC(50)<100μg/ml for cytotoxicity, and IC(50)<130μg/ml for anti-inflammatory reaction. The majority of the extracts tested (69%) exhibited potency in at least one of these three types of activity. This is the first report describing promising antiplasmodial activity (IC(50)<15μg/ml) for Psiadia dentata DCM extract and Terminalia bentzoe MeOH bark extract. NO inhibition assay revealed seven interesting plants, described for the first time as anti-inflammatory: Aphloia theiformis, Buddleja salviifolia, Eupatorium riparium, Hiptage benghalensis, Psiadia arguta, Psiadia dentata, and Scutia commersonii. Finally, anti-proliferative activity was observed for two endemic species, Geniostoma borbonicum and Nuxia verticillata. CONCLUSION Using the criterion of endemism as part of the criteria for traditional medicinal use raises the chances of finding original active principles. In our case, 86% of the endemic plants tested displayed pharmacological interest.

ANTIPROTOZOAL ACTIVITY OF SESQUITERPENES FROM JASONIA GLUTINOSA

Two sesquiterpene alcohols, [11 R]-eudesm-4(14)-en-5ß,11,12-triol ( 1 ) and [11R]-eudesm-4(14)-en-5a,11-12-triol ( 2 ), from Jasonia glutinosa aerial parts (Asteraceae), have been tested using an in vitro technique against Leishmania donovani (promastigote forms) and Plasmodium falciparum . Sesquiterpene 1 was not effective at the assayed concentrations. Sesquiterpene 2 was found to be active against Leishmania donovani and Plasmodium falciparum .

Quinovic acid glycosides from Nauclea diderrichii

From the bark of Nauclea diderrichii (de Wild) Merr. seven saponins were isolated and characterized by 2D-NMR and FABMS. These compounds are quinovic acid glycosides previously reported for the Rubiaceae, six of them are described for the first time in this drug.

New antiplasmodial alkaloids from Stephania rotunda

ETHNOPHARMACOLOGICAL RELEVANCE Stephania rotunda Lour. (Menispermaceae) is a creeper growing in many countries of Asia and commonly found in the mountainous areas of Cambodia. As a folk medicine, it has been mainly used for the treatment of fever and malaria. The pharmacological activity is mostly due to alkaloids. Thus the aim of this study is to isolate new bioactive alkaloids from Stephania rotunda and to evaluate their in vitro antiplasmodial activity. MATERIALS AND METHODS Alkaloids were isolated and identified from dichloromethane and aqueous extracts using a combination of flash chromatography, high performance liquid chromatography, mass spectrometry and nuclear magnetic resonance. The purified compounds were tested for in vitro antiplasmodial activity on chloroquine-resistant W2 strain of Plasmodium falciparum. RESULTS A new aporphine alkaloid named vireakine (2) along with two known alkaloids stephanine (1) and pseudopalmatine (8), described for the first time in Stephania rotunda, and together five known alkaloids tetrahydropalmatine (3), xylopinine (4), roemerine (5), cepharanthine (6) and palmatine (7) were isolated and identified. The structure of the new alkaloid was established on the basis of 1D and 2D NMR experiments and mass spectrometry. The compounds were evaluated for their in vitro antiplasmodial and cytotoxic activities. All tested compounds showed significant antiplasmodial activities with IC(50) ranged from 1.2 μM to 52.3 μM with a good selectivity index for pseudopalmatine with IC(50) of 2.8 μM against W2 strain of Plasmodium falciparum and IC(50)>25 μM on K562S cells. CONCLUSIONS This study provides evidence to support the use of Stephania rotunda for the treatment of malaria and/or fever by the healers. Alkaloids of the tuber exhibited antiplasmodial activity and particularly cepharanthine and pseudopalmatine.

Antimalarial compounds from the aerial parts of Flacourtia indica (Flacourtiaceae)

AIM OF THE STUDY In the Comoros Islands, the aerial parts of Flacourtia indica are used in traditional medicine to treat malaria. Because of the important use of this plant, the phytochemistry of the aerial parts was investigated. MATERIALS AND METHODS Three compounds were isolated from the decoction of this plant material, pyrocatechol, homaloside D and poliothrysoside. The in vitro antiplasmodial activity on the chloroquine-resistant strain (W2) of Plasmodium falciparum and the cytotoxicity on two complementary human cell lines (THP1, HepG2), of AcOEt extract obtained after liquid/liquid extraction of the decoction and pure compounds, were evaluated. RESULTS The poliothrysoside isolated from the AcOEt extract presented a strong antiplasmodial activity (IC(50)=7.4 microM) and a good selectivity index (>28) similar to chloroquine. CONCLUSION This study reports for the first time antiplasmodial activity for Flacourtia indica, for its AcOEt extract and the three major constituents and confirms its traditional use.

New amide alkaloid from the aerial part of Piper capense L.f. (Piperaceae).

Together with apigenine dimethylether and piperchabamide A, a new amide alkaloid, Kaousine and the Z form of antiepilepsirine were isolated from the aerial part of Piper capense L.f (Piperaceae). Their structures were elucidated by spectrometric methods and their in vitro antiparasitic activities were evaluated on Plasmodium falciparum.

Cytotoxic Activity of Alkaloids Isolated from Stephania rotunda In vitro cytotoxic activity of cepharanthine

Three major alkaloids: cepharanthine (1), tetrahydropalmatine (2) and xylopinine (3) isolated from Stephania rotunda tuber were investigated for their cytotoxic activity in a panel of human cancer cells (HT29, LS174T, SW620 and HepG2) using MTT assay. In the present study, cepharanthine (1) exerted potent cytotoxicity against colon and hepatoma cancer cell lines with IC(50) values between 2.4 and 5.3 microM while tetrahydropalmatine (2) and xylopinine (3) displayed weak cytotoxicity. In addition, the mutagenic activity of cepharanthine (1) was investigated using a modified liquid incubation technique of the Salmonella/microsomal assay. This alkaloid (1) was found to be non-mutagenic for doses up to 8.2 microM.

Genotoxic and clastogenic activity of saponins extracted from Nauclea bark as assessed by the micronucleus and the comet assays in Chinese Hamster Ovary cells

ETHNOPHARMACOLOGICAL RELEVANCE Bark extracts of Nauclea latifolia, Nauclea diderrichii, Nauclea pobeguinii and Nauclea vandergutchii are used in traditional medicine in West and South Africa for the treatment of fevers, diarrhea and malaria. AIM OF THE STUDY To estimate the possible long-term toxicity and genotoxicity of plant extracts (dichloromethane, methanol, water/methanol, water) and saponins. MATERIALS AND METHODS The clastogenicity of plant extracts and saponins was assessed by the micronucleus assay performed on Chinese Hamster Ovary cells. The DNA-damaging activity of saponin mixture was assessed by the comet assay on Chinese Hamster ovary cells. RESULTS Hydromethanolic extracts from Nauclea latifolia, Nauclea diderrichii and Nauclea pobeguinii exhibited a significant clastogenic/aneugenic activity without S9 mix. The hydromethanolic extract from Nauclea diderrichii was the most clastogenic/aneugenic fraction with a Minimal Active Concentration (MAC) of 23.1 μgm L(-1). It was submitted to a separation step leading to six main saponins identified as quinovic acid glycosides (saponins A, D, E, G, J, K). None of the isolated saponins exerted a significant clastogenic/aneugenic activity by the micronucleus assay, however a mixture made with equal quantities of each of the six saponins exhibited a direct genotoxic/clastogenic activity as assessed by both the micronucleus assay and the comet assay on Chinese Hamster Ovary cells. CONCLUSION Saponins present in the hydromethanolic extracts of Nauclea induced synergistic in vitro DNA-damage and chromosome mutations in mammalian cells. This genotoxic activity was probably due to the capacity of Nauclea saponins to reduce cell defense against oxidative stress through the inhibition of glutathione-S-transferase activity.