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The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl.
Dissertation (MSc (Biochemistry))--University of Pretoria,2024.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2024
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| _version_ | 1867613574608715776 |
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| access_status_str | Open Access |
| author2 | Mosa, Rebamang A |
| author_browse | Mosa, Rebamang A |
| author_facet | Mosa, Rebamang A |
| collection | Thesis |
| dc_rights_str_mv | © 2023 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. |
| description | Dissertation (MSc (Biochemistry))--University of Pretoria,2024. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/95427 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:38:18.923Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/95427 The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl. Mosa, Rebamang A naleli.ramasia@gmail.com Ramasia, Naleli Nthabiseng UCTD Atherosclerosis Cholesterol trafficking Lipid peroxidation Foam cell formation Triterpenes Dissertation (MSc (Biochemistry))--University of Pretoria,2024. Atherocardiovascular diseases (ACVDs) are considered among the major causes of death in South Africa and worldwide. Hypercholesterolemia, which is the main major risk factor of atherosclerosis, increases the occurrence of ACVDs. Despite the use of the current drugs to treat ACVDs, the continuous increase in morbidity and mortality rates associated with atherocardiovascular events indicate limitations of the current treatment regime. Medicinal plants are known to contain numerous compounds with various bioactivities including antioxidant capacity and lipid lowering properties. The triterpenoid compounds (ARM-2 and RA-5) isolated from Protorhus longifolia (Benrh.) Engl. stem bark have shown promising bioactivities such as inhibiting dietary cholesterol digestion and potential to regulate the endogenous pathway of cholesterol biosynthesis. These properties play a vital part in the amelioration of hypercholesterolemia. This study investigated the antiatherogenic potential of ARM-2 and RA-5. The computational and wet lab experiments were implemented to investigate the preventative properties of the compounds against oxidative modification of LDL and foam cell formation that underlie the progression of atherosclerotic plaque. The in silico molecular docking of the compounds against some proteins involved in cholesterol trafficking, and their ADMET properties were determined. In vitro analysis of potential bioactivities of the compounds was determined through antioxidant assays (ABTS, DPPH, ferric reducing power and ORAC), and inhibition of the CuSO4 mediated LDL oxidation. The oxidized LDL-induced foam cell formation experiment was carried out to determine the inhibitory activity of the compounds against foam cell formation in RAW 264.7 cells. Molecular docking of the compounds indicated poor binding affinity against CD36, SR-A1, ABCA-1 and sPLA2 in contrast to strong binding affinities against ABCG-1, ACAT-1 and LOX-1. Both compounds were predicted to have promising ADMET properties and drug-likeness depicted by high intestinal absorption and no inhibition observed for the cytochrome P450 isoform. The triterpenes showed poor free radical scavenging activity (ABTS and DPPH) and reducing power but indicated good activity against peroxyl free radicals. Inhibition of oxidative modification of LDL was observed by decreased CD and MDA formation by both compounds at 500 μM. However, the compounds were unable to inhibit sPLA2 activity. Except for RA-5 at 25 μM, high viability of the cells was observed following their exposure to both triterpenes. The compounds decreased intracellular lipid droplet formation, ultimately resulting in decreased foam cell formation by 14% and 10% for ARM-2 (25 μM) and RA-5 (10 μM) respectively. Overall, the results from the study revealed that both triterpenes possess bioactive properties to inhibit oxidative modification of LDL and decrease foam cell formation, highlighting their antiatherogenic potential. University of Pretoria Postgraduate Bursary. National Research Foundation. Biochemistry MSc (Biochemistry) Unrestricted Faculty of Natural and Agricultural Sciences SDG-03: Good health and well-being 2024-04-02T09:07:24Z 2024-04-02T09:07:24Z 2024-05 2024-01 Dissertation * A2024 http://hdl.handle.net/2263/95427 DOI: https://doi.org/10.25403/UPresearchdata.25512082.v1 10.25403/UPresearchdata.25512082 en © 2023 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. application/pdf University of Pretoria |
| spellingShingle | UCTD Atherosclerosis Cholesterol trafficking Lipid peroxidation Foam cell formation Triterpenes The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl. |
| title | The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl. |
| title_full | The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl. |
| title_fullStr | The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl. |
| title_full_unstemmed | The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl. |
| title_short | The Antiatherogenic Potential of Two triterpenes from Protorhus longifolia stem bark (Benrh.) Engl. |
| title_sort | antiatherogenic potential of two triterpenes from protorhus longifolia stem bark benrh engl |
| topic | UCTD Atherosclerosis Cholesterol trafficking Lipid peroxidation Foam cell formation Triterpenes |
| url | http://hdl.handle.net/2263/95427 |