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

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH 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. / AFRIKAANSE 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.

Identiferoai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/96680
Date04 1900
CreatorsMugari, Mufaro Buhlebenkosi
ContributorsSwart, Amanda C., Swart, Pieter, Stellenbosch University. Faculty of Science. Dept. of Biochemistry.
PublisherStellenbosch : Stellenbosch University
Source SetsSouth African National ETD Portal
Languageen_ZA
Detected LanguageUnknown
TypeThesis
Formatxvii, 130 pages : colour illustrations
RightsStellenbosch University

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