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Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis
Kgatla, T. M. 2025. Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.a...
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| Language: | English |
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Stellenbosch : Stellenbosch University
2025
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| _version_ | 1867614087313096704 |
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| access_status_str | Open Access |
| author | Kgatla, Thato Mmathapelo |
| author2 | Maarman, Gerald |
| author_browse | Kgatla, Thato Mmathapelo Maarman, Gerald |
| author_facet | Maarman, Gerald Kgatla, Thato Mmathapelo |
| author_sort | Kgatla, Thato Mmathapelo |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Kgatla, T. M. 2025. Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/d70588d8-bdf1-4cf7-b45d-390cc22d85eb |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/132223 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:46:27.621Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/132223 Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis Kgatla, Thato Mmathapelo Maarman, Gerald Marais, Erna Johnson, Rabia Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Medical Physiology. Rooibos tea -- Therapeutic use Mitochondrial pathology Heart -- Cytology Angiotensin II -- Physiological effect UCTD Kgatla, T. M. 2025. Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/d70588d8-bdf1-4cf7-b45d-390cc22d85eb Thesis (PhD)--Stellenbosch University, 2025. ENGLISH ABSTRACT: Background: Cardiovascular disease (CVD) remains a global health challenge, with its pathophysiology characterized by hypertrophy, oxidative stress, and mitochondrial dysfunction. These processes are interconnected, where oxidative stress and mitochondrial dysfunction drive cardiac hypertrophy which subsequently enhances apoptosis and exacerbates myocardial damage. Existing medications present several adverse effects, highlighting the need for novel therapeutic approaches. Aspalathus linearis, commonly known as Rooibos (RB), has demonstrated antioxidant properties, and the potential to enhance mitochondrial function. Emerging evidence suggests that RB may mitigate CVD risk factors, however, the underlying molecular mechanisms require further investigation. Therefore, this project aimed to (1) investigate the novel effects of RB in a cardiomyoblast model of Angiotensin-II (Ang-II) induced hypertrophy and apoptosis, and (2) to further elucidate its impact on mitochondrial regulation. Methods: H9C2 cardiomyoblasts were cultured and treated for 48 hours as follows: Ang- II (20 μM), RB extract (100 μg/mL), Ang-II+RB and Ang- II+Losartan (Los) (10 μM). Post-treatment, cell size and cell viability were assessed. Antioxidant activity, particularly superoxide dismutase (SOD) and catalase (CAT) activity were evaluated, and lipid peroxidation was assessed. Additionally, the expression of hypertrophic and apoptotic signalling proteins was examined. Mitochondrial respiration parameters, ATP levels, and citrate synthase activity were analysed. Autophagy and caspase-3 activity, and the expression of mitochondrial proteins were assessed. Furthermore, we investigated the effects of co-treatment with a metallothionein (MT) inducer and inhibitor on RB-mediated effects on cell size and viability. Results: Ang-II increased cell size, reduced cell viability, elevated malondialdehyde (MDA) levels, enhanced GSK3β inhibition, inhibited the expression of mTOR, increased the expression of Bax, and decreased the expression of BAD. Co-treatment with RB reduced cell size, improved cell viability, increased the expression of NFAT1, reduced the inhibition of GSK3β, enhanced SOD activity, increased the expression of mTOR and reduced the expression of Bax. Ang-II increased mitochondrial respiration parameters (routine respiration, leak, complex-I-linked OXPHOS, cytochrome-c response, Electron transport system (ETS) capacity, the S and F-pathway's contribution to ETS, and complex-II's contribution to ETS). Ang-II also increased autophagy, caspase-3 activity, and VDAC1 expression, and reduced ATP levels and the inhibition of Drp1. Co-treatment with RB restored leak respiration, complex I-linked OXPHOS, and the contribution of the F- pathway to ETS capacity. Co-treatment with RB increased ATP levels, reduced caspase-3 activity and the expression of VDAC1, and enhanced Drp1 inhibition. Furthermore, in the presence of an MT inhibitor, the protective effects of RB on cell size and cell viability were slightly reduced, whereas in the presence of an MT inducer, the effects were enhanced, particularly on cell size. Conclusion: Our study is the first to demonstrate the protective effects of RB against Ang-II-induced hypertrophy and apoptosis, and RB achieves this by augmenting antioxidant enzyme activity and by influencing hypertrophic signalling pathways. Moreover, RB attenuated apoptotic responses, improved mitochondrial dynamics (particularly fission), and restored mitochondrial respiratory pathways. The data on the MT inhibitor and inducer suggest that RB may rely on naturally occurring MTs within cells to exert its protective effects. This study further underscores the significance of mitochondria in RB-induced protection. AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar. Doctoral 2025-05-30T08:39:58Z 2025-05-30T08:39:58Z 2025-03 Thesis https://scholar.sun.ac.za/handle/10019.1/132223 en Stellenbosch University xx, 240 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Rooibos tea -- Therapeutic use Mitochondrial pathology Heart -- Cytology Angiotensin II -- Physiological effect UCTD Kgatla, Thato Mmathapelo Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis |
| title | Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis |
| title_full | Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis |
| title_fullStr | Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis |
| title_full_unstemmed | Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis |
| title_short | Delineating the novel effects of Aspalathus linearis (Rooibos) on mitochondrial regulation in an in vitro model of angiotensin-II induced hypertrophy and apoptosis |
| title_sort | delineating the novel effects of aspalathus linearis rooibos on mitochondrial regulation in an in vitro model of angiotensin ii induced hypertrophy and apoptosis |
| topic | Rooibos tea -- Therapeutic use Mitochondrial pathology Heart -- Cytology Angiotensin II -- Physiological effect UCTD |
| url | https://scholar.sun.ac.za/handle/10019.1/132223 |
| work_keys_str_mv | AT kgatlathatommathapelo delineatingthenoveleffectsofaspalathuslinearisrooibosonmitochondrialregulationinaninvitromodelofangiotensiniiinducedhypertrophyandapoptosis |