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

Developing theory-informed behaviour change interventions to implement evidence into practice : a systematic approach using the Theoretical Domains Framework

PMID: 22531013 [PubMed - indexed for MEDLINE] PMCID: PMC3443064 Free PMC ArticlePeer reviewedPublisher PD

Natural products published in 2009 from plants traditionally used to treat malaria

Malaria is a major parasitic disease and is responsible for almost one million deaths each year in Africa. There is an urgent need to discover new active compounds. Nature and particularly plants are a potential source of new antimalarial drugs since they contain a quantity of metabolites with a great variety of structures and pharmacological activities. This review covers the compounds with antiplasmodial activity isolated from plants which have been published during 2009 organized according to their phytochemical classes. Details are given for substances with IC (50) values ≤ 11 µM. Sixty-seven references are identified

Evaluation de l'activité antiparasitaire de plantes utilisées en médecine traditionnelle au Bénin et identification de principes actifs

Parasitic diseases are still responsible for many health problems. Among them, African trypanosomiasis or sleeping sickness caused by Trypanosoma brucei, malaria transmitted by Plasmodium species of which the most dangerous is Plasmodium falciparum and leishmaniasis. Plant biodiversity and knowledge of traditional healing allow, as it was the case for artemisinin, to open new ways in the field of therapeutic. In this work, we analyzed the activity of several plants from Benin selected by ethnobotanical and bibliographical studies. These plants are used in traditional medicine as antimalarials. Crude extracts from powders of leaves, twigs, roots or aerial parts were prepared by maceration. These extracts were studied for their antiparasitic activities by in vitro tests on Plasmodium falciparum, Trypanosoma brucei brucei and Leishmania mexicana mexicana. In addition, cytotoxicities were analysed to determine the selectivity of crude extracts. The dichloromethane extracts of Keetia leucantha were selected and known antiparasitc compounds were identified and quantified by LC-MS. As they could not account for the total activity observed, we isolated by bioguided fractionation several triterpenic esters, vanillin derivatives, a sterol and a coumarin. The structure determination of isolated compounds was performed by NMR studies and high resolution mass spectrometry. We also identified and quantified by GC-MS the major volatile constituents from the essential oil of leaves. The isolated compounds were studied in vitro for their antiplasmodial, antitrypanosomal and antileishmanial activities. Several of them showed a sub-micromolar antiplasmodial activity, including some triterpenic esters which are 10 to 100 times more active than ursolic acid. In addition, we tested the in vivo antimalarial activity of some extracts: the dichloromethane extract of twigs of Keetia leucantha showed 40.7 % inhibition in mice infected by Plasmodium berghei at 100 mg/kg/day and the total aqueous extract a 30.8% inhibition at 200 mg/kg/day. Furthermore, some compounds with good antitrypanosomal activity were studied to understand their mode of action by in vitro tests on the bloodstream and procyclic forms of trypanosomes, by studies of parasite motility and by inhibitory tests on a glycolytic enzyme. The results showed an inhibition of the activity of glyceraldehyde-3-phosphate dehydrogenase trypanosomale (GAPDH) at low concentration for some of them, the most active being oleanolic acid.Les maladies parasitaires posent encore de nombreux problèmes de santé. Parmi celles-ci, citons la trypanosomiase africaine ou maladie du sommeil dont l’agent responsable est le Trypanosoma brucei, la malaria transmise par le Plasmodium dont l’espèce la plus dangeureuse est le Plasmodium falciparum et la leishmaniose. La richesse de la biodiversité végétale et la connaissance des thérapeutiques traditionnelles sont susceptibles, comme ce fut le cas pour l'artémisinine, d’ouvrir de nouvelles voies dans le domaine de la thérapeutique antipaludéenne, c’est pourquoi nous avons analysé l’activité de plusieurs plantes. Celles-ci ont été sélectionnées par des études ethnobotaniques et bibliographiques au Bénin parmi celles utilisées en médecine traditionnelle comme antipaludiques. Des extraits bruts à partir des poudres de feuilles, de tiges, de racines ou de la partie aérienne ont été réalisés par macérations. Ces extraits ont été étudiés pour leur activité antiparasitaire par des tests in vitro sur Plasmodium falciparum, sur Trypanosoma brucei et Leishmania mexicana mexicana. De plus, des tests de cytotoxicité ont été réalisés afin de déterminer la sélectivité des extraits. Les extraits dichlorométhanes de Keetia leucantha ont été sélectionnés. Certains composés connus ont été identifiés directement sur l’extrait brut par LC-MS et certains d’entre eux ont également été quantifiés. A partir de l’extrait dichlorométhane des poudres de feuilles et de tiges du Keetia leucantha, nous avons isolé par fractionnement bioguidé ou chimioguidé plusieurs acides et esters triterpéniques, un stérol et une coumarine. La détermination structurale des molécules isolées a été réalisée par des études RMN et les masses exactes ont été déterminées en spectrométrie de masse haute résolution. Nous avons également identifié et quantifié les principaux composés volatils issus de l’huile essentielle par GC-MS. Les molécules ainsi isolées ont été étudiées pour leur activité antiplasmodiale, antileishmaniale et antitrypanosomale in vitro et plusieurs d’entre elles ont montré une activité antiplasmodiale sub-micromolaire, notamment certains esters triterpéniques 10 à 100 fois plus actifs que l’acide ursolique. De plus, nous avons vérifié l’activité antimalarique in vivo : l’extrait dichloromethane des tiges du Keetia leucantha a ainsi montré une inhibition de 40,7 % chez les souris infestées par Plasmodium berghei à une dose de 100 mg/kg/jour et l’extrait aqueux total une inhibition de 30,8 % à une dose de 200 mg/kg/jour. Certains composés présentant une bonne activité antitrypanosomale ont été étudiés afin de mieux comprendre leur mode d’action et ce, par des tests in vitro sur la forme sanguine et procyclique du trypanosome, par des études de motilité parasitaire ainsi que par des tests d’inhibition enzymatique. Les résultats ont montré une inhibition à faible concentration de l’activité de la glycéraldéhyde-3-phosphate déshydrogénase trypanosomale (GAPDH).(FARM 3) -- UCL, 201

Natural Products and Tropical Diseases

Tropical diseases encompass all diseases that occur solely, or principally, in the tropics. In practice, the term is often taken to refer to infectious diseases that thrive in hot, humid conditions, such as malaria, leishmaniasis, schistosomiasis, onchocerciasis, lymphatic filariasis, Chagas disease, African trypanosomiasis, and dengue. Neglected tropical diseases affect about 1 billion people, primarily poor populations living in tropical and subtropical climates, and in 2008, malaria caused nearly one million deaths, mostly among African children (WHO, 2011)[*]. There is an urgent need to discover new treatments against these ailments or to kill their vectors because of the development of resistance and/or the side effects or costs of available treatments. Furthermore, as people suffering from these diseases are often from developing countries and have low incomes, the economical interest is not high for the research and development of new molecules. Therefore, most people still rely on traditional medicine for their prevention or treatment. As plants are a recognized source of new medicines with great potential, Planta Medica has decided to publish a special issue on natural products and tropical diseases to report advances in this area. Reviews compiled in this special issue deal with different aspects of prevention and treatment of tropical diseases as well as tests and targets for the discovery of such compounds from nature. They also include overviews of effective extracts, fractions, or isolated compounds from plants or marine sources, or improved traditional phytomedicines used against well-known diseases as malaria and others as Buruli ulcer