Identification of anti-HIV compounds in Helichrysum species (Asteraceae) by means of NMR-based metabolomic guided fractionation

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dc.contributor.advisor Meyer, J.J.M. (Jacobus Johannes Marion)
dc.contributor.coadvisor Maharaj, Vinesh J.
dc.contributor.postgraduate Heyman, Heino Martin
dc.date.accessioned 2014-06-17T13:09:14Z
dc.date.available 2014-06-17T13:09:14Z
dc.date.created 2014-04-09
dc.date.issued 2014 en_US
dc.description Thesis (PhD)--University of Pretoria, 2014. en_US
dc.description.abstract The plant kingdom contributes significantly to the natural products that are used for the treatment of a large number of ailments and disease across the globe. Included in these species is the Helichrysum genus (Asteraceae), which comprises of more then 600 species across Africa of which 244 species are found in South Africa. Helichrysum species are used in many cases for the treatment of coughs, colds, fever, infection, headaches, menstrual pain and are also very popular for wound dressing due to their potential antibacterial properties. The most common Helichrysum species used in traditional medicine and for several medicinal purposes are H. cymosum, H. odoratissimum, H. petiolare and H. nudifolium. Previously published research has shown that several of the Helichrysum species do have antimicrobial activity with the most relevant to this study being the discovery of antiviral activity of H. aureonitens against herpes simplex virus type 1 (HSV-1) as well as the reports of anti-HIV (human immunodeficiency virus) activity of several Helichrysum species. With this knowledge, a more in-depth study was initiated to identify the possible active constituents in South African Helichrysum species against HIV. Due to the need to speed up drug discovery especially against epidemic diseases like HIV, this study investigated a new tool (nuclear magnetic resonance (NMR) – based metabolomics) to speed up drug discovery form natural products especially when anti-viral constituents are investigated. odoratissimum, H. petiolare and H. nudifolium. Previously published research has shown that several of the Helichrysum species do have antimicrobial activity with the most relevant to this study being the discovery of antiviral activity of H. aureonitens against herpes simplex virus type 1 (HSV-1) as well as the reports of anti-HIV (human immunodeficiency virus) activity of several Helichrysum species. With this knowledge, a more in-depth study was initiated to identify the possible active constituents in South African Helichrysum species against HIV. Due to the need to speed up drug discovery especially against epidemic diseases like HIV, this study investigated a new tool (nuclear magnetic resonance (NMR) – based metabolomics) to speed up drug discovery form natural products especially when anti-viral constituents are investigated. In this study very promising anti-HIV results were obtained from several aqueous extracts (1:1 methanol/water) using a full virus model i.e. Helichrysum populifolium (IC50 12 μg/ml), H. appendiculatum (IC50 17 μg/ml), H. cymosum ssp. clavum (IC50 19 μg/ml), H. oxyphyllum (IC50 19 μg/ml) and H. cymosum ssp. cymosum (IC50 21 μg/ml). With the use of NMR-based metabolomics and multivariate data analysis (MVA) the specific characteristic that differentiated the active extracts from the non-active extracts was identified by making use of Orthogonal Projections to Latent Structures – Discriminant Analysis (OPLS-DA). This characteristic was then used as a “blue print” or “fingerprint” to guide the process of fractionation and purification. H. populifolium showed the highest anti-HIV activity and thus was selected as the candidate extract for further analysis. After a very quick and simple chromatographic fractionation process, seven fractions were compared against the activity profile by making use of their NMR profiles, which then visually indicated which of the fractions had the highest similarity. Fraction 6 had the most similar “fingerprint”. The compounds of this active fraction were then identified with the use of liquid chromatography – ion trap – time of flight (LC-IT-TOF) for quick identification. The analysis revealed the presence of five chlorogenic type compounds, 3,4-dicaffeoyl quinic acid (DCQA), 3,5-DCQA, 4,5-DCQA, 1,3,5- tricaffeoyl quinic acid (TCQA) and 5-malonyl-1,3,4-TCQA of which several are well known to have anti-HIV activity ranging from 0.85μM to 12μM. We were thus able to show with this study the possibility of using NMR-based metabolomics guided fractionation to guide the process of fractionation and identification from an active characteristic profile to the active constituents within the active H. populifolium extract. en_US
dc.description.availability unrestricted en_US
dc.description.department Plant Science en_US
dc.description.librarian gm2014 en_US
dc.identifier.citation Heyman, HM 2013, Identification of anti-HIV compounds in Helichrysum species (Asteraceae) by means of NMR-based metabolomic guided fractionation, PhD thesis, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/40273> en_US
dc.identifier.other D14/4/117/gm en_US
dc.identifier.uri http://hdl.handle.net/2263/40273
dc.language.iso en en_US
dc.publisher University of Pretoria en_ZA
dc.rights © 2013 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_US
dc.subject Helichrysum en_US
dc.subject Asteraceae en_US
dc.subject HIV en_US
dc.subject Helichrysum populifolium en_US
dc.subject Metabolomics en_US
dc.subject Caffeoyl quinic acid en_US
dc.subject UCTD en_US
dc.title Identification of anti-HIV compounds in Helichrysum species (Asteraceae) by means of NMR-based metabolomic guided fractionation en_US
dc.type Thesis en_US


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