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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Kola acuminata proanthocyanidins: A class of anti-trypanosomal compounds effective against Trypanosoma brucei
International Journal for Parasitology, Volume 35, No. 1, Year 2005
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Description
Human African trypanosomiasis is undergoing an alarming rate of recrudescence in many parts of sub-Saharan Africa. Yet, there is no successful chemotherapy for the disease due to a limited number of useful drugs, side effects and drawbacks of the existing medication, as well as the development of drug resistance by the parasite. Here we describe a new lead anti-trypanosomal compound isolated from Kola acuminata (Makasu). We purified a proanthocyanidin by chromatographic procedures and confirmed its homogeneity and structure by Nuclear Magnetic Resonance and Matrix-Assisted Laser Desorption Ionisation Time-of-Flight mass spectrometry, respectively. In vitro, this compound potently induced growth arrest and lysis of bloodstream form trypanosomes in a dose- and time-dependent manner. In a mouse model, it exhibited a trypanostatic effect that extended the life of infected, treated animals up to 8 days post-infection against the 4 days for infected, untreated animals. The proanthocyanidin showed a low cytotoxicity against mammalian cells, whereas treated-BF showed massive enlargement of their flagellar pocket and lysosome-like structures caused by an intense formation of multivesicular bodies and vesicles within these organelles. The observed ultrastructural alterations caused rupture of plasma membranes and the release of cell contents, indicative of a necrotic process rather than a programmed cell death. Interestingly, the proanthocyanidin acted against BF but not procyclic form trypanosomes. This new anti-trypanosomal compound should be further studied to determine its efficacy and suitability as an anti-trypanosomal drug and may be used as a tool to define novel specific drug targets in BF trypanosomes. © 2004 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Kubata, Bruno Kilunga
Japan, Suita
Osaka Bioscience Institute
United States, Arlington
United States Army
Nagamune, Kisaburo
Japan, Suita
Research Institute for Microbial Diseases
Murakami, Nobutoshi
Japan, Suita
Osaka University
Merkel, Patrick
Germany, Tubingen
Eberhard Karls Universität Tübingen
Kabututu, Zakayi
Japan, Suita
Osaka Bioscience Institute
Japan, Suita
Research Institute for Microbial Diseases
Martin, Samuel K.
United States, Arlington
United States Army
Kalulu, Taba M.
Congo
Kinshasa University
Mustakuk, Haq
Japan, Suita
Osaka University
Yoshida, Mitsuru
Japan, Tsukuba
Food Research Institute, Naro
Ohnishi-Kameyama, Mayumi
Japan, Tsukuba
Food Research Institute, Naro
Kinoshita, Taroh
Japan, Suita
Research Institute for Microbial Diseases
Duszenko, Michael
Germany, Tubingen
Eberhard Karls Universität Tübingen
Urade, Yoshihiro
Japan, Suita
Osaka Bioscience Institute
Statistics
Citations: 42
Authors: 13
Affiliations: 7
Identifiers
Doi:
10.1016/j.ijpara.2004.10.019
ISSN:
00207519
Research Areas
Cancer