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Fourteen metabolites, isolated from phytopathogenic and toxigenic fungi, were evaluated for their in vitro antigrowth activity for six distinct cancer cell lines, using the MTT colorimetric assay. Bislongiquinolide (1) and dihydrotrichodimerol (5), which belong to the bisorbicillinoid structural class, displayed significant growth inhibitory activity against the six cancer cell lines studied, while the remaining compounds displayed weak or no activity. The data show that 1 and 5 have similar growth inhibitory activities with respect to those cancer cell lines that display certain levels of resistance to pro-apoptotic stimuli or those that are sensitive to apoptosis. Quantitative videomicroscopy analysis revealed that 1 and 5 exert their antiproliferative effect through cytostatic and not cytotoxic activity. The preliminary results from the current study have stimulated further structure-activity investigations with respect to the growth inhibitory activity of compounds belonging to the bisorbicillinoid group.

Based on an ethnobotanical survey, 41 Guinean plant species widely used in the traditional treatment of fever and/or malaria were collected. From these, 74 polar and apolar extracts were prepared and tested for their in vitro antiprotozoal activity along with their cytotoxicity on MRC-5 cells. A potent activity (IC50 < 5 µg/mL) was observed for Terminalia albida, Vismia guineensis, Spondias mombin, and Pavetta crassipes against Plasmodium falciparum; for Pavetta crassipes, Vismia guineensis, Guiera senegalensis, Spondias mombin, Terminalia macroptera, and Combretum glutinosum against Trypanosoma brucei brucei; for Bridelia ferruginea, G. senegalensis, V. guineensis, P. crassipes, and C. glutinosum against Trypanosoma cruzi. Only the extract of Tetracera alnifolia showed a good activity (IC50 8.1 µg/mL) against Leishmania infantum. The selectivity index of the active samples varied from 0.08 to > 100. These results may validate at least in part the traditional use of some of the plant species.

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A number of traditional Guinean plant species used against malaria/fever showed, in addition to their antiplasmodial properties and antimicrobial activity. The fact that some plant species are involved in the traditional treatment of malaria/fever without any antiplasmodial evidence may be justified by their antimicrobial activities.

BackgroundThe development of Plasmodium resistance to the last effective anti-malarial drugs necessitates the urgent development of new anti-malarial therapeutic strategies. To this end, plants are an important source of new molecules. The objective of this study was to evaluate the anti-malarial effects of Terminalia albida, a plant used in Guinean traditional medicine, as well as its anti-inflammatory and antioxidant properties, which may be useful in treating cases of severe malaria.MethodsIn vitro antiplasmodial activity was evaluated on a chloroquine-resistant strain of Plasmodium falciparum (K-1). In vivo efficacy of the plant extract was measured in the experimental cerebral malaria model based on Plasmodium berghei (strain ANKA) infection. Mice brains were harvested on Day 7–8 post-infection, and T cells recruitment to the brain, expression levels of pro- and anti-inflammatory markers were measured by flow cytometry, RT-qPCR and ELISA. Non-malarial in vitro models of inflammation and oxidative response were used to confirm Terminalia albida effects. Constituents of Terminalia albida extract were characterized by ultra‐high performance liquid chromatography coupled with high resolution mass spectrometry. Top ranked compounds were putatively identified using plant databases and in silico fragmentation patterns.ResultsIn vitro antiplasmodial activity of Terminalia albida was confirmed with an IC50 of 1.5 μg/mL. In vivo, Terminalia albida treatment greatly increased survival rates in P. berghei-infected mice. Treated mice were all alive until Day 12, and the survival rate was 50% on Day 20. Terminalia albida treatment also significantly decreased parasitaemia by 100% on Day 4 and 89% on Day 7 post-infection. In vivo anti-malarial activity was related to anti-inflammatory properties, as Terminalia albida treatment decreased T lymphocyte recruitment and expression of pro-inflammatory markers in brains of treated mice. These properties were confirmed in vitro in the non-malarial model. In vitro, Terminalia albida also demonstrated a remarkable dose-dependent neutralization activity of reactive oxygen species. Twelve compounds were putatively identified in Terminalia albida stem bark. Among them, several molecules already identified may be responsible for the different biological activities observed, especially tannins and triterpenoids.ConclusionThe traditional use of Terminalia albida in the treatment of malaria was validated through the combination of in vitro and in vivo studies.

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The presence of these constituents in Hymenocardia acida leaves and Uapaca togoensis stem bark may at least in part support their traditional use against hypertension in Guinea.