Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals.

Ebiloma, G. U., Igoli, J. O., Katsoulis, E., Donachie, A.-M., Eze, A., Gray, A. I. and de Koning, H. P. (2017) Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals. Journal of Ethnopharmacology, 202, pp. 256-264. (doi: 10.1016/j.jep.2017.03.028) (PMID:28336470)

Abstract

Ethnopharmacological relevance: Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. Aim of the study: To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Material and methods: Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Results: Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38 µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC50 of 1.58 µg/mL. None of the isolated compounds displayed toxicity towards Human Embryonic Kidney cells at concentrations up to 400 µg/mL. In addition, the isolated compounds were active against Leishmania mexicana, as well as against T. congolense. Conclusion: We have isolated a clerodane compound from Polyalthia longifolia that shows low toxicity, no cross-resistance with current treatments, and promising activity against both human-infective and veterinary Trypanosoma species.

• Item Type: Articles
• Additional Information: This study was supported by the Tertiary Education Trust Fund (TETFUND-2011/2012), Federal Government of Nigeria, in the form of a studentship to G.U.E.
• Keywords: Antiparasite chemotherapy, Leishmania mexicana, Trypanosoma brucei, ethnopharmacology, extracts, purified compounds.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Donachie, Ms Anne Marie and Ebiloma, Mr Godwin and De Koning, Professor Harry
• Authors: Ebiloma, G. U., Igoli, J. O., Katsoulis, E., Donachie, A.-M., Eze, A., Gray, A. I., and de Koning, H. P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Ethnopharmacology
• Publisher: Elsevier
• ISSN: 0378-8741
• ISSN (Online): 1872-7573
• Published Online: 20 March 2017
• Copyright Holders: Copyright © 2017 Elsevier B.V.
• First Published: First published in Journal of Ethnopharmacology 202: 256-264
• Publisher Policy: Reproduced in accordance with the publisher copyright policy