Nmr-based metabolomic study of medicinal plants used against malaria and the isolation of bioactive alkaloids

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dc.contributor.advisor Meyer, J.J.M. (Jacobus Johannes Marion) en
dc.contributor.postgraduate Bapela, M.J. (Mahwahwatse Johanna) en
dc.date.accessioned 2016-07-01T10:33:13Z
dc.date.available 2016-07-01T10:33:13Z
dc.date.created 2016-04-18 en
dc.date.issued 2016 en
dc.description Thesis (PhD)--University of Pretoria, 2016. en
dc.description.abstract Despite the significant advances achieved in lessening the burden of malaria and other tropical diseases in recent years, protozoal infections remain a major cause of mortality in many developing countries, with malaria accounting for a large proportion of the recorded mortality. The main aim of this study was to bioprospect indigenous plant species for novel antiplasmodial plant products by means of NMRbased metabolomics. In this study, an ethnobotanical criterion was followed in collecting twenty indigenous plant species used to treat malaria or its symptoms by Vha-Venda people living in Mutale Municipality of Limpopo Province, South Africa. Plant samples were extracted in dichloromethane:50% methanol (1:1), separated into polar and nonpolar fractions, and tested on Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani and Plasmodium falciparum. Plant extracts were correspondingly subjected to an antiproliferative bioassay against mammalian skeletal myoblast cells. The current study is the first scientific account on the significant antileishmanial efficacy (IC50 ? 5 ?g/ml) of Bridelia mollis (Phyllanthaceae), Vangueria infausta subsp. infausta (Rubiaceae), Syzygium cordatum (Myrtaceae) and Xylopia parviflora (Annonaceae), as well as high antitrypanosomal activity (IC50 = 3.45 ?g/ml) of Albizia versicolor (Fabaceae). Ten plant extracts exhibited significant in vitro antiplasmodial activity (IC50 ? 5 ?g/ml), with Tabernaemontana elegans (IC50 = 0.331 ?g/m and IC50 = 0.834 ?g/m) and V. infausta subsp. infausta (IC50 = 1.84 ?g/ml) being the best samples. This is the first scientific report to document significant antiplasmodial activity of extracts from T. elegans. The findings of this study substantiate the rationale for adopting an ethnopharmacological approach when bioprospecting medicinal plants for antiplasmodial compounds. Dichloromethane extracts were subjected to 1H NMR-based metabolomic analysis, where each crude extract was reconstituted in CDCl3, analysed on a Varian 600 MHz spectrometer and the acquired 1H NMR spectra were then analysed collectively using multivariate data analysis (MDA). Principal Component Analysis (PCA) could not separate the analysed profiles according to the detected antiplasmodial bioactivity. Application of supervised Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) on the 1H NMR profiles resulted in a discrimination pattern that could be correlated to the observed antimalarial bioactivity. A contribution plot generated from the OPLS-DA scoring plot illustrated the classes of compounds responsible for the observed grouping. Further phytochemical analyses were conducted on lipophilic extracts of T. elegans and V. infausta subsp. infausta. These best candidates were fractionated, purified and identified based on conventional chromatographic and spectroscopic techniques. Two known indole alkaloids isolated from T. elegans, were identified as dregamine and tabernaemontanine. The antiplasmodial activity of these acyl indole alkaloids has previously been established and ranges from moderate to good. Three compounds were isolated from V. infausta subsp. infausta of which two were identified as friedelin (IC50 = 3.01 ?g/ml) and morindolide (IC50 = 18.5 ?g/ml). While these compounds have been previously identified, this is the first account of their occurrence in the genus Vangueria and their antiplasmodial activity. An unidentified compound with significant antiplasmodial activity (IC50 = 0.143 ?g/ml) was also isolated. The study demonstrated the potential of discovering novel antiplasmodial scaffolds from medicinal plants. en
dc.description.availability Unrestricted en
dc.description.degree PhD en
dc.description.department Plant Science en
dc.identifier.citation Bapela, M(J 2016, Nmr-based metabolomic study of medicinal plants used against malaria and the isolation of bioactive alkaloids, PhD Thesis, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/53513> en
dc.identifier.other A2016 en
dc.identifier.uri http://hdl.handle.net/2263/53513
dc.language.iso en en
dc.publisher University of Pretoria en_ZA
dc.rights © 2016, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. en
dc.subject UCTD en
dc.title Nmr-based metabolomic study of medicinal plants used against malaria and the isolation of bioactive alkaloids en
dc.type Thesis en


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