Characterization and isolation of anti-HIV and latency reversal agents for the development of a herbal mixture of Gnidia sericocephala, Senna italica, Sclerocarya birrea and Pentanisia prunelloides

dc.contributor.advisorMaharaj, Vinesh J.
dc.contributor.coadvisorDr. Dashnie, Naidoo-Maharaj
dc.contributor.emailu17350884@tuks.co.zaen_US
dc.contributor.postgraduateTembeni, Babalwa
dc.date.accessioned2023-03-31T06:47:58Z
dc.date.available2023-03-31T06:47:58Z
dc.date.created2023
dc.date.issued2022
dc.descriptionThesis (PhD)--University of Pretoria, 2022.en_US
dc.description.abstractTwo non-daphnane diterpenoids were isolated as biomarkers and later identified using one and two dimensional nuclear magnetic resonance (1D and 2D NMR) as lasioerin and lasiocephalin. The preparative purification of the active fractions resulted in isolation of five daphnane diterpenoids (yuanhuacine A, yuanhuacine, a cis 2′′/3′′ isomer of gnididin, yuanhuajine and gniditrin) with viral inhibition properties as well as latency reversal activity. The compound yuanhuacine A and the mixture of yuanhuacine and the cis 2′′/3′′ isomer of gnididin showed in vitro HIV replication inhibition by > 80% at 0.08 μg/ml. Furthermore, yuanhuacine A inhibited a subtype C virus replication in peripheral blood mononuclear cells (PBMC) with a half maximal effective concentration (EC50) of 0.03 μM without cytotoxicity. The mixture of compounds, yuanhuacine and the cis 2′′/3′′ isomer of gnididin in an in vitro assay also reversed HIV latency by 16.7-fold lower concentrations than the control prostratin and also reversed HIV latency in primary helper T cells (CD4+ T cells) from combinatory anti- retroviral therapy (cART)-suppressed donors with HIV similar to the protein kinase C (PKC) activator prostratin but at 6.7-fold lower concentrations. These results suggests that G. sericocephala, yuanhuacine A and the mixture of yuanhuacine and a cis 2′′/3′′ isomer of gnididin act as anti-HIV agents to improve cART efficacy and support HIV cure efforts in resource-limited regions.en_US
dc.description.availabilityUnrestricteden_US
dc.description.degreePhDen_US
dc.description.departmentChemistryen_US
dc.description.sponsorshipNational Research Foundation.en_US
dc.description.sponsorshipDepartment of Science and Innovation.en_US
dc.identifier.citation*en_US
dc.identifier.doi10.25403/UPresearchdata.22363796en_US
dc.identifier.otherS2023
dc.identifier.urihttp://hdl.handle.net/2263/90297
dc.identifier.uriDOI: https://doi.org/10.25403/UPresearchdata.22353796.v1
dc.language.isoenen_US
dc.publisherUniversity of Pretoria
dc.rights© 2022 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.
dc.subjectUCTDen_US
dc.subjectMedicinal plantsen_US
dc.subjectYuanhuacine Aen_US
dc.subjectNatural products chemistryen_US
dc.subjectNuclear magnetic resonanceen_US
dc.subjectMass directed purificationen_US
dc.titleCharacterization and isolation of anti-HIV and latency reversal agents for the development of a herbal mixture of Gnidia sericocephala, Senna italica, Sclerocarya birrea and Pentanisia prunelloidesen_US
dc.typeThesisen_US

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