BackgroundThe current treatment of onchocerciasis relies on the use of ivermectin which is only microfilaricidal and for which resistant parasite strains of veterinary importance are increasingly being detected. In the search for novel filaricides and alternative medicines, we investigated the selective activity of crude extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi, a model parasite for O. volvulus. These plants are used to treat the disease in North West Cameroon.MethodsSixteen crude extracts were prepared from various parts of M. discoidea and H. africanum using different organic solvents. The filaricidal activities were determined in vitro. Cytotoxicity of the active extracts was assessed on monkey kidney epithelial cells in vitro and the selectivity indices (SI) of the extracts determined. Acute toxicity of the promising extracts was investigated in mice.ResultsFour out of the 16 extracts showed microfilaricidal activity based on motility reduction, whereas, none showed macrofilaricidal activity based on the MTT/formazan assay. The methylene chloride extract of H. africanum leaves (HLC) recorded the lowest IC50 of 31.25 μg/mL and an IC100 of 62.5 μg/mL. The SI for the active extracts ranged from 0.5 - 2.63. No form of acute toxicity was observed in mice. Phytochemical analysis revealed the presence of anthraquinones, sterols and terpenoids in the promising extracts.ConclusionsThe non-polar extracts of M. discoidea and H. africanum are potential sources of new microfilaricidal lead compounds, and the results support their use in traditional medicine.

BackgroundMalaria is a major public health threat in Africa, and traditional medicine continues to play a key role in its control especially in rural areas. A bioassay-guided fractionation was carried out in order to evaluate the anti-malarial potential and the safety of the methanol extract of the Hypericum lanceolatum stem bark.MethodsThe anti-plasmodial activity was assayed by the lactate dehydrogenase method (pLDH) against the multidrug-resistant W2mef laboratory strain, and a field isolate (SHF4) of Plasmodium falciparum. Cytotoxicity tests were carried out using the LLC-MK2 monkey kidney epithelial cells.ResultsFive compounds were isolated from the most active and least cytotoxic ethylacetate sub-extract: betulinic acid (HLT1), 2,2',5,6'-tetrahydroxybenzophenone (HLT2), 5-hydroxy-3-methoxyxanthone (HLT3), 3-hydroxy-5-methoxyxanthone (HLT4) and HLT0 (yet to be identified). Three of the tested compounds presented significant anti-plasmodial activities (with 50% inhibitory concentration, IC50 < 5 μM), with 5-hydroxy-3-methoxyxanthone exerting the highest activity, followed by HLT0 and betulinic acid. All the compounds with significant anti-plasmodial activity were non-cytotoxic, except betulinic acid which showed a 50% cytotoxic concentration, CC50 of 25 μg/mL.ConclusionsThese findings justify the use of H. lanceolatum stem bark as anti-malarial by traditional healers of Western Cameroon, and could constitute a good basis for further studies towards development of new drug candidates or phytomedicines for malaria.

The aims of the present study were to identify the compounds responsible for the anti-malarial activity of Dacryoedes edulis (Burseraceae) and to investigate their suitability as leads for the treatment of drug resistant malaria. Five compounds were isolated from ethyl acetate and hexane extracts of D. edulis stem bark and tested against 3D7 (chloroquine-susceptible) and Dd2 (multidrug-resistant) strains of Plasmodium falciparum, using the parasite lactate dehydrogenase method. Cytotoxicity studies were carried out on LLC-MK2 monkey kidney epithelial cell-line. In silico analysis was conducted by calculating molecular descriptors using the MOE software running on a Linux workstation. The “drug-likeness” of the isolated compounds was assessed using Lipinski criteria, from computed molecular properties of the geometry optimized structures. Computed descriptors often used to predict absorption, distribution, metabolism, elimination and toxicity (ADMET) were used to assess the pharmacokinetic profiles of the isolated compounds. Antiplasmodial activity was demonstrated for the first time in five major natural products previously identified in D. edulis, but not tested against malaria parasites. The most active compound identified was termed DES4. It had IC50 values of 0.37 and 0.55 µg/mL, against 3D7 and Dd2 respectively. In addition, this compound was shown to act in synergy with quinine, satisfied all criteria of “Drug-likeness” and showed considerable probability of providing an antimalarial lead. The remaining four compounds also showed antiplasmodial activity, but were less effective than DES4. None of the tested compounds was cytotoxicity against LLC-MK2 cells, suggesting their selective activities on malaria parasites. Based on the high in vitro activity, low toxicity and predicted “Drug-likeness” DES4 merits further investigation as a possible drug lead for the treatment of malaria.

In order to assess the potential of the stem bark of Kigelia africana (Lam.) Benth as source of new anti-malarial leads, n-hexane and ethyl acetate (EtOAc) extracts and four compounds isolated from the stem bark were screened in vitro against the chloroquine-resistant W-2 and two field isolates of Plasmodium falciparum using lactate dehydrogenase assay. The products were also tested for their cytotoxicity on LLC/MK2 monkey kidney cells. The EtOAc extract exhibited a significant antiplasmodial activity (IC(50) = 11.15 μg/mL on W-2; 3.91 and 4.74 μg/mL on field CAM10 and SHF4 isolates, respectively), whereas the n-hexane fraction showed a weak activity (IC(50) = 73.78 μg/mL on W-2 and 21.85 μg/mL on SHF4). Three out of the four compounds showed good activity against all the three different parasite strains (IC(50) <5 μM). Specicoside exhibited the highest activity on W-2 (IC(50) = 1.54 μM) followed by 2β, 3β, 19α-trihydroxy-urs-12-en-28-oic acid (IC(50) = 1.60 μM) and atranorin (IC(50) = 4.41 μM), while p-hydroxycinnamic acid was the least active (IC(50) =53.84 μM). The EtOAc extract and its isolated compounds (specicoside and p-hydroxycinnamic acid) were non-cytotoxic (CC(50) > 30 μg/mL), whereas the n-hexane extract and two of its products, atranorin and 2β, 3β, 19α-trihydroxy-urs-12-en-28-oic acid showed cytotoxicity at high concentrations, with the last one being the most toxic (CC(50) = 9.37 μg/mL). These findings justify the use of K. africana stem bark as antimalaria by traditional healers of Western Cameroon, and could constitute a good basis for further studies towards development of new leads or natural drugs for malaria.

Medicinal plants play a key role in malaria control in Africa, especially in remote areas where health facilities are limited. In order to assess their acclaimed potentials, eleven extracts were prepared from seven selected plants commonly used in Western Cameroon, and tested both for their antiplasmodial activity and cytotoxicity. The antiplasmodial activity was assessed using Lactate Dehydrogenase Assay (pLDH) and the cytotoxicity estimated on LLC-MK2 monkey kidney epithelial cells. Seven extracts from five different plants were significantly active, with very weak or no cytotoxicity. The Dacryodes edulis leaves showed the highest activity (IC50 of 6.45 μg/mL on 3D7 and 8.2 μg/mL on DD2) followed by the leaves of Vernonia amygdalina (IC50 of 8.72 and 11.27 μg/mL on 3D7 and DD2 resp.) and roots of V. amygdalina (IC50 of 8.72 μg/mL on 3D7), Coula edulis leaves (IC50 of 13.80 μg/mL and 5.79 μg/mL on 3D7 and DD2 resp.), Eucalyptus globulus leaves (IC50 of 16.80 μg/mL and 26.45 μg/mL on 3D7 and DD2) and Cuviera longiflora stem bark (IC50 of 20.24 μg/mL and 13.91 μg/mL on 3D7 and DD2). These findings justify the use of five of the seven plants in malaria treatment by traditional healers of Western Cameroon.