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The inhibitory effect of rooibos on cytochromes P450 and downstream in vitro modulation of steroid hormones

dc.contributor.advisorSwart, Amanda C.en_ZA
dc.contributor.advisorSwart, Pieteren_ZA
dc.contributor.authorMugari, Mufaro Buhlebenkosien_ZA
dc.contributor.otherStellenbosch University. Faculty of Science. Dept. of Biochemistry.en_ZA
dc.date.accessioned2015-05-20T09:13:45Z
dc.date.available2015-05-20T09:13:45Z
dc.date.issued2015-04en
dc.identifier.urihttp://hdl.handle.net/10019.1/96680
dc.descriptionThesis (MSc)--Stellenbosch University, 2015.
dc.description.abstractENGLISH ABSTRACT: This study describes: 1. Substrate binding assays investigating the effects of methanolic extracts of unfermented and fermented Rooibos on the binding of natural substrates to ovine adrenal microsomal and mitochondrial P450 enzymes, demonstrating the interference of substrate binding in the presence of the Rooibos extracts. 2. The effects of selected flavonoids (quercetin, rutin and aspalathin) on the binding of natural substrates to ovine adrenal microsomal and mitochondrial P450 enzymes, demonstrating interference of substrate binding in the presence of the flavonoid compounds. 3. Substrate conversion assays in non-steroidogenic COS-1 cells to investigate the effects of methanolic extracts of unfermented and fermented Rooibos on the activity of key steroidogenic P450 enzymes (CYP17A1, CYP21A2, CYP11B1, and CYP11B2), demonstrating inhibition of the catalytic activity in the presence of Rooibos extracts. 4. The effects of selected flavonoids on the substrate conversion of the aforementioned key steroidogenic enzymes expressed in COS-1 cells. 5. An investigation of the effect of methanolic extracts of unfermented and fermented Rooibos on steroid hormone production in human adrenal H295R cells under basal and stimulated conditions, demonstrating the modulating effects of unfermented and fermented Rooibos extracts. Basal and stimulated steroid hormone production was decreased in the presence of unfermented and fermented Rooibos.en_ZA
dc.description.abstractAFRIKAANSE OPSOMMING: Hierdie studie beskryf: 1. Die gebruik van substraatbindings-essais om die effek van metanoliese ekstrakte, van gefermenteerde- en ongefermenteerde Rooibos, op die binding van die natuurlike substrate aan skaap adrenale mikrosomale en -mitochondriale P450 ensieme te bepaal. Daar is getoon dat die ekstrakte 'n beduidende inhiberende effek op ensiemsubstraatinteraksie gehad het. 2. Die die inhiberende effek van geselekteerde flavonoïede (kwersetien, rutien and aspalatien) op die binding van die natuurlike substrate aan skaap adrenale mikrosomale en -mitochondriale P450 ensieme. 3. Die gebruik van substraatomsettings-essais in nie-steroïedogeniese COS-1 selle, om die effek van gefermenteerde- en ongefermenteerde Rooibos ekstrakte op die aktiwiteit van die steroïedogeniese P450 ensieme (CYP17A1, CYP21A2, CYP11B1, and CYP11B2) se katalitiese aktiwiteit te bepaal. Daar kon aangetoon word dat die katalitise aktiwiteite van bg. ensieme beduidend beïnvloed word deur die Rooibos ekstrakte. 4. Die gebruik van substraatomsettings-essais in nie-steroïedogeniese COS-1 selle, om die effek van geselekteerde flavonoïede op die aktiwiteit van bogenoemde steroïedogeniese P450 ensieme te bepaal. 5. 'n Ondersoek na die invloed van metanoliese ekstrakte van gefermenteerde- en ongefermenteerde Rooibos op steroïedhormoon biosintese in die menslike adrenale H295R-selmodel. Die ondersoek, onder basale en gestimuleerde toestande, het getoon dat beide Rooibosekstrakte in bogenoemde toestande steroïedhormoon produksie geinhibeer het.af_ZA
dc.format.extentxvii, 130 pages : colour illustrations
dc.language.isoen_ZAen_ZA
dc.publisherStellenbosch : Stellenbosch University
dc.subjectCytochrome P-450en_ZA
dc.subjectSteroid hormonesen_ZA
dc.subjectRooibos tea -- Therapeutic useen_ZA
dc.subjectUCTDen_ZA
dc.titleThe inhibitory effect of rooibos on cytochromes P450 and downstream in vitro modulation of steroid hormonesen_ZA
dc.typeThesisen_ZA
dc.rights.holderStellenbosch University


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