Antileishmanial Activity of Leaf and Inflorescence Extracts of Globularia alypum L. and Phytochemical Analysis

Leishmaniasis is one of the pathologies qualified as “neglected tropical diseases”, due to the lack of investment from the pharmaceutical industry in developing more efficient molecules against this disease. Our work focused on the antileishmanian potential of Globularia alypum L.; a shrub belonging to the spontaneous flora of Algeria, known for its uses in traditional medicine. The bioactivity of two essential oils and six crude extracts of different polarities, obtained respectively from the leaves and inflorescences of the plant, was evaluated in vitro on the promastigote form of four species of Leishmania: L. donovani, L. infantum, L. killicki and two strains of L. major. The parasite growth inhibition tests were performed using RPMI-1640 enriched culture medium. Percent inhibition and half-maximal Inhibitory Concentrations (IC50) were determined after 72 h of incubation. The estimate of the Selectivity Index (SI) of the active extracts was carried out by the complementary analysis of their cytotoxicity on transformed human monocytic cell line. In addition, the extracts that revealed the best leishmanicidal effects were analyzed for their chemical composition using Gas Chromatography coupled with Mass Spectroscopy. Our main results demonstrated for the first time the existence of a significant leishmanicidal activity of etheric extracts of leaves (EE.1) and inflorescences of the plant (EE.2) on the promastigote form of the parasitic strains. The best IC50s observed are those determined for the L. donovani strain: 89.7 and 24.8 μg/ml, respectively for the etheric extracts EE.1 and EE.2. The latter presents respectively SI greater than 2.8 and 10.1 toward L. donovani, which suggests that their toxicity would be selective to the parasite. Phytochemical analysis of EE.1 and EE.2 allowed the identification of molecules that could be at the origin of the observed results. This preliminary work on the valorization of the plant resource and associated ethnobotanical knowledge contributes to broadening the prospects for the fight against leishmaniases with a high epidemic and mortality potential.