In vitro antileishmanial and cytotoxicity activities of essential oils from Haplophyllum tuberculatum A. Juss leaves, stems and aerial parts

Background: Plants used for traditional medicine produce diverse and complex secondary metabolites exhibiting various medicinal properties. The medicinal plant Haplophyllum tuberculatum is used by native people against malaria and parasitic infections. Methods: In this study and in order to contribute for the search of new natural drugs for leishmaniasis, the essential oils of H. tuberculatum leaves, stems and aerial parts (leaves+stems) collected in two different periods, 2013 and 2015, and their components by GC/FID and GC/MS analyses were investigated. Those collected in 2013 were also re-analyzed two years later. The extracted oils were screened in vitro for anti-leishmanial activity on Leishmania mexicana mexicana (L.m.m.) promastigotes and cytotoxicity on the Chinese Hamster Ovary (CHO) cell line. Limonene (1.5 – 8%), its isomers (R- (+)-limonene and S-(-)-limonene), linalool and octanol were also tested. Results: Results showed that the chemical composition varied according to the year of collection. Though major compounds remain almost the same, qualitative and quantitative variations in the composition of the EOs can be observed between the two years of collection, with some minor compounds identified only in one type of samples. Variation in the composition were also observed in the re-analyzed volatile oils, showing stability concerns. The essential oils and R-(+)-limonene showed moderate anti-leishmanial activity. Their IC50 range from 6.48 to 50.28 μg/ml. Cytotoxicity assays for theses volatile extracts, R- (+)-limonene and S- (-)-limonene on CHO cells showed relatively potent cytotoxicity with a selectivity index <10. Their CC50 range from 27.79 to 82.56 μg/ml. Conclusions: The findings of the present study demonstrated that H. tuberculatum might not be considered as a natural source for production of new anti-leishmanial agents without further analyzing its eventual in vivo toxicity as well as that of major pure compounds

Evaluation of antiparasitic potential of plants used in traditional medicine, of their bioactive triterpenic components and derivatives

Parasitic infections, as malaria, African trypanosomiasis and cutaneaous leishmaniasis, remain one of the main global public health concerns nowadays, despite ongoing efforts. In the crucial research for new antiparasitic treatments, we focused our work on plants used in traditional medicine and their bioactive components. Firstly, we showed, using mice models, the antiparasitic potential and absence of acute toxicity of three plants traditionally used in Benin: Byrsocarpus coccineus (on Trypanosoma brucei), Keetia leucantha (on Plasmodium) and Carpolobia lutea (on both parasites). Given their in vivo antimalarial efficacy, Keetia leucantha twigs were chosen for further researches. The decoction safety was evaluated in different in vivo models (zebrafish embryo, mice acute and repeated-dose toxicity tests) and a part of its antimalarial activity was attributed to the presence of tannins. We then developed validated quantification methods in plant and in plasma for previously identified eight triterpenic esters (27-O-(E/Z)-feruloyl/coumaroyl-oxy-oleanolic/ursolic acids). We also proved their selective in vivo antiplasmodial activities at 50 mg/kg and their involvement in the efficacy of the crude dichloromethane extract of K. leucantha twigs, with other triterpenic acids. Exploring their mechanism of action, we identified an enzyme implied in the essential haemoglobin degradation pathway, as one potential selective target. Finally, a series of triterpenic acids and esters were screened and compared for in vitro selective antiparasitic activities. Among tested compounds, some esters showed promising antitrypanosomal activity (IC50 near 2 µM). However, some tested compounds did not improve parasitaemia evolution and survival in an acute trypanosomiasis mice model. This work contributes to the valorization of traditional medicine and to the search for natural antiprotozoal compounds.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201

Evaluation of antiparasitic potential of plants used in traditional medicine, of their bioactive triterpenic components and derivatives

Parasitic infections, as malaria, African trypanosomiasis and cutaneaous leishmaniasis, remain one of the main global public health concerns nowadays, despite ongoing efforts. In the crucial research for new antiparasitic treatments, we focused our work on plants used in traditional medicine and their bioactive components. Firstly, we showed, using mice models, the antiparasitic potential and absence of acute toxicity of three plants traditionally used in Benin: Byrsocarpus coccineus (on Trypanosoma brucei), Keetia leucantha (on Plasmodium) and Carpolobia lutea (on both parasites). Given their in vivo antimalarial efficacy, Keetia leucantha twigs were chosen for further researches. The decoction safety was evaluated in different in vivo models (zebrafish embryo, mice acute and repeated-dose toxicity tests) and a part of its antimalarial activity was attributed to the presence of tannins. We then developed validated quantification methods in plant and in plasma for previously identified eight triterpenic esters (27-O-(E/Z)-feruloyl/coumaroyl-oxy-oleanolic/ursolic acids). We also proved their selective in vivo antiplasmodial activities at 50 mg/kg and their involvement in the efficacy of the crude dichloromethane extract of K. leucantha twigs, with other triterpenic acids. Exploring their mechanism of action, we identified the aminopeptidase PfA-M17, implied in the essential haemoglobin degradation pathway, as one potential selective target. Finally, a series of triterpenic acids and esters were screened and compared for in vitro selective antiparasitic activities. Among tested compounds, some semi-synthesized 3-O-aromatic esters showed promising antitrypanosomal activity (IC50 near 2 µM). However, hydrocinnamic and ortho-fluorophenylpropionic ursolic acids, as well as ursolic acid did not improve parasitaemia evolution and survival in an acute trypanosomiasis mice model. This work contributes to the valorization of traditional medicine and to the search for natural antiprotozoal compounds.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 201

Antimalarial Terpenic Compounds Isolated from Plants Used in Traditional Medicine (2010–July 2016)

Malaria is an infectious tropical disease mainly affecting children and sub-Saharan Africa, being one of the major death causes with almost half of the world population at risk. Therefore and to face increasing parasite resistance to available treatments, there is an urgent need to discover new antimalarial drugs. Nature and mostly plants are a resourceful supplier of potential active metabolites, as shown by the successful example of the sesquiterpene lactone: artemisinin. Terpenoids are occurring widely in nature and display a lot of biological activities among which antiplasmodial effects. This review is a compilation of terpenic compounds isolated from plants with moderate (2 μ M < IC50 _ 11 μ M) to strong (IC50 _ 2 μ M) activity against different strains of Plasmodium published from 2010 to July 2016. Forty-seven references are identifi e

In vivo anti-malarial activity and toxicity studies of triterpenic esters isolated form Keetia leucantha and crude extracts.

BACKGROUND: Considering the need for new anti-malarial drugs, further investigations on Keetia leucantha (Rubiaceae), an in vitro antiplasmodial plant traditionally used to treat malaria, were carried out. This paper aimed to assess the in vivo anti-malarial efficacy of K. leucantha triterpenic esters previously identified as the most in vitro active components against Plasmodium falciparum and their potential toxicity as well as those of anti-malarial extracts. RESULTS: These eight triterpenic esters and the major antiplasmodial triterpenic acids, ursolic and oleanolic acids, were quantified in the twigs dichloromethane extract by validated HPLC-UV methods. They account for about 19% of this extract (16.9% for acids and 1.8% for esters). These compounds were also identified in trace in the twigs decoction by HPLC-HRMS. Results also showed that extracts and esters did not produce any haemolysis, and were devoid of any acute toxicity at a total cumulative dose of 800 and 150 mg/kg respectively. Moreover, esters given intraperitoneally at 50 mg/kg/day to Plasmodium berghei-infected mice showed a very significant (p < 0.01) parasitaemia inhibition (27.8 ± 5.4%) on day 4 post-infection compared to vehicle-treated mice. CONCLUSIONS: These results bring out new information on the safety of K. leucantha use and on the identification of anti-malarial compounds from its dichloromethane extract. Its activity can be explained by the presence of triterpenic acids and esters which in vivo activity and safety were demonstrated for the first time

In Vitro Anti-Leishmanial Activity of Essential Oils Extracted from Vietnamese Plants.

Leishmania mexicana is one of the pathogens causing cutaneous leishmaniasis which is associated with patient morbidity. In our researches for new safe and effective treatments, thirty-seven essential oils (EOs) extracted from Vietnamese plants were screened in vitro for the first time on Leishmania mexicana mexicana(Lmm) promastigotes at the maximum concentration of 50 nL/mL. Active EOs were also analyzed for cytotoxicity on mammalian cell lines (WI38, J774) and their selectivity indices (SI) were calculated. Their composition was determined by GC-MS and GC-FID. Our results indicated that EOs extracted from Cinnamomum cassia, Zingiber zerumbet, Elsholtzia ciliata and Amomum aromaticum, possessed a moderate anti-leishmanial activity, with IC50 values of 2.92 ± 0.08, 3.34 ± 0.34, 8.49 ± 0.32 and 9.25 ± 0.64 nL/mL respectively. However, they also showed cytotoxicity with SI 10. It contained 86.5% eugenol, which was demonstrated to be effective on Lmm with IC50 of 2.57 ± 0.57 nL/mL and not toxic on mammalian cells, explaining the observed activity