Investigating the efficacy and underlying mechanism of cardioprotection afforded by rooibos (aspalathus linearis) in angiotensin-ii induced cardiac hypertrophy & apoptosis
| dc.contributor.advisor | Marais, Erna | en_ZA |
| dc.contributor.advisor | Maarman, Gerald | en_ZA |
| dc.contributor.advisor | Strijdom, Hans | en_ZA |
| dc.contributor.advisor | Lopes, John | en_ZA |
| dc.contributor.author | Sithelo, Pamela | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology. | en_ZA |
| dc.date.accessioned | 2021-02-26T14:30:33Z | |
| dc.date.accessioned | 2021-04-21T14:39:51Z | |
| dc.date.available | 2021-02-26T14:30:33Z | |
| dc.date.available | 2021-04-21T14:39:51Z | |
| dc.date.issued | 2021-03 | |
| dc.description | Thesis (MSc)--Stellenbosch University, 2021. | en_ZA |
| dc.description.abstract | Purpose:Rooibos (RB) has been reported to confer cardioprotection, but the underlying mechanisms are not fully elucidated. Furthermore, RB has never been tested againstcardiac hypertrophy and apoptosis. Therefore, this study investigated the efficacy and underlying mechanisms of RB-induced cardioprotection in a model of angiotensin-II (Ang-II) induced cardiomyocyte hypertrophy & apoptosis. Methods:Six groups of H9c2cardiomyoblasts were either exposed to 2% FBS supplemented DMEM (control), Ang-II (20μM), RB (100μg/ml), Losartan (10μM) and co-treatment with RB + Ang-II or Ang-II + Losartan for 48 hrs. Cell viability, ATP levels, and hypertrophy and apoptosis signalling were measured with Western blotting. Cell size and mitochondrial membrane potential were measured using JC-1. Mitochondrial oxidative stress was measured with aconitase assay. Results:Ang-II induced hypertrophy as well as apoptosis in H9c2 cardiomyoblasts by increasing cell size and upregulating growth signalling pathways, while decreasing cell viability, up-regulating of pro-apoptotic markers (Bax and cleaved caspase-3) and downregulating anti-apoptotic Bcl-2. In addition, Ang-II decreased mitochondrial membrane potential and ATP levels. RB co-treatment effectively antagonized Ang-II-induced hypertrophy and apoptosis of H9c2 cells. This was mediated by reducing cell size and dephosphorylating growth signalling pathways such as ERK 1/2, PKB, mTOR, Calcineurin and GSK-3ß. RB also increased cell viability by increasing Bcl-2, decreasing Bax and cleaved caspase-3and thereby, inhibiting apoptosis.The administration of RB prevented depolarization of mitochondrial membrane potential and increased ATP activity. RB also enhanced the expression of mitochondrial respiratory chain complex IV and V, probably through the enhancement of mitochondrial biogenesis and the electron transfer system. Conclusion:To our knowledge, the current study is the first to show that RB attenuates Ang-II induced cardiomyoblast hypertrophy and apoptosis by improving mitochondrial parameters and restoring GSK-3 beta and Bcl-2 signalling. | en_ZA |
| dc.description.abstract | Doel:Daar word berig dat Rooibos (RB) kardiobeskerming verleen, maar die onderliggende meganismes is nog nie volledig toegelig nie. Verder is RB nog nooit getoets in kardiale hipertrofie en apoptose nie. Daarom het hierdie studie die doeltreffendheid en onderliggende meganismes van RB-geïnduseerde kardiobeskerming in 'n model van angiotensien-II (Ang-II) geïnduseerde kardiomiosiet-hipertrofie en -apoptose ondersoek. Metodes:Ses groepe H9c2-kardiomioblaste is blootgestel aan 2% FBS aangevulde DMEM (kontrole), Ang-II (20 μM), RB (100 μg / ml), Losartan (10 μM) en gesamentlike behandeling met RB + Ang-II of Ang-II + Losartan vir 48 uur. Sellewensvatbaarheid, ATP-vlakke en hipertrofie en apoptose-sein is gemeet met Western blotting. Selgrootte en mitochondriale membraanpotensiaal is met behulp van JC-1 gemeet. Mitochondriale oksidatiewe stres is gemeet met akonitase-assai. Resultate:Ang-II ïnduseerd hipertrofie sowel as apoptose in H9c2-kardiomyoblaste deur die selgrootte te verhoog en die groei van seinpaaie op te reguleer, terwyl dit die lewensvatbaarheid van die selle verminder, die pro-apoptotiese merkers (Bax en gekliefde caspase-3) opreguleer en die anti-apoptotiese Bcl-2 afreguleer. Verder het Ang-II die mitochondriale membraanpotensiaal en ATP-vlakke verlaag. Medebehandeling met RB het Ang-II-geïnduseerde hipertrofie en apoptose van H9c2-selle effektief geantagoniseer. Dit is bemiddel deur die vermindering van die selgrootte en die defosforilering van seinpaaie vir groei soos ERK 1/2, PKB, mTOR, Calcineurin en GSK-3ß. RB het ook die lewensvatbaarheid van die selle verhoog deur Bcl-2 te verhoog, Bax en gekliefde caspase-3 te verminder en dus apoptose te inhibeer. Die toediening van RB het depolarisasie van mitochondriale membraanpotensiaal voorkom en ATP-aktiwiteit verhoog. RB het ook die uitdrukking van mitochondriale respiratoriese kettingkompleks IV en V verbeter, waarskynlik deur die verbetering van mitochondriale biogenese en die elektronoordragstelsel. Gevolgtrekking:Na ons mening is die huidige studie die eerste om aan te toon dat RB Ang-II geïnduseerde kardiomioblast hipertrofie en apoptose attenueer/onderdruk, deur mitochondriale parameters te verbeter en GSK-3 beta en Bcl-2 seine te herstel. | af_ZA |
| dc.description.version | Masters | en_ZA |
| dc.format.extent | 164 pages | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/10019.1/110089 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | en_ZA |
| dc.rights.holder | Stellenbosch University | en_ZA |
| dc.subject | Hypertrophy, Apoptosis | en_ZA |
| dc.subject | UCTD | en_ZA |
| dc.subject | Aspalathus linearis | en_ZA |
| dc.subject | Cardiac hypertrophy | en_ZA |
| dc.subject | Apoptosis | en_ZA |
| dc.title | Investigating the efficacy and underlying mechanism of cardioprotection afforded by rooibos (aspalathus linearis) in angiotensin-ii induced cardiac hypertrophy & apoptosis | en_ZA |
| dc.type | Thesis | en_ZA |