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The inhibition of adrenal steroidogenic enzymes and modulation of glucocorticoid levels in vitro and in vivo by aspalathus linearis (rooibos)Schloms, Lindie 04 1900 (has links)
Thesis (PhD)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: This study describes:
• the influence of a methanolic extract of unfermented Rooibos and five major
Rooibos flavonoids, aspalathin, nothofagin, rutin, orientin and vitexin, on the
activities of key adrenal steroidogenic enzymes - cytochrome P450 17β-
hydroxylase/17,20-lyase (CYP17A1), 3β-hydroxysteroid dehydrogenase
• the development of a novel UPLC-MS/MS method for the separation and
quantification of 21 adrenal steroid metabolites;
• the influence of Rooibos and aforementioned flavonoids on adrenal steroid
hormone production in H295R cells - a human adrenal carcinoma cell line
expressing the enzymes catalysing the production of mineralocorticoids,
glucocorticoids and adrenal androgens, assayed under both basal (normal)
and forskolin-stimulated (stressed) conditions;
• the influence of Rooibos on the inter-conversion between cortisol and
cortisone by 11βHSD1 and 11βHSD2 expressed in CHO-K1 cells;
• the influence of Rooibos consumption on circulating steroid hormone levels
and ratios in male Wistar rats;
• the influence of Rooibos consumption on circulating steroid hormone levels
and ratios in male and female human test subjects at risk for developing
cardiovascular disease.
(3βHSD2), cytochrome P450 21-hydroxylase (CYP21A2) and cytochrome
P450 11β-hydroxylase (CYP11B1), expressed in non-steroidogenic COS-1
cells; / AFRIKAANSE OPSOMMING: Hierdie studie beskryf:
• die invloed van metanoliese ekstrakte van ongefermenteerde Rooibos en vyf
van die hoof flavonoïedverbindings in Rooibos, aspalatien, notofagien, rutien,
oriëntien en viteksien, op die aktiwiteite van ensieme wat steroïedbiosintese
in die bynier kataliseer – sitochroom P450 17α-hidroksilase/17,20-liase
(CYP17A1), 3β-hidroksisteroïed dehidrogenase (3βHSD2), sitochroom P450
21-hidroksilase (CYP21A2) en sitochroom P450 11β-hidroksilase (CYP11B1),
uitgedruk in nie-steroïed produserende COS-1 selle;
• die ontwikkeling van ‘n geskikte UPLC-MS/MS metode vir die skeiding en
kwantifisering van 21 steroïedmetaboliete in die bynier;
• die invloed van Rooibos en die bg. flavonoïede op steroïedproduksie in
H295R selle – ‘n menslike bynier kanker sellyn gekenmerk deur die
ekspressie van die steroidogeniese ensieme wat die produksie van
mineralokortikoïede, glukokortikoïede en bynierandrogene kataliseer, geanaliseer
onder beide basale (normale) en forskoliengestimuleerde
(gestresde) kondisies;
• die invloed van Rooibos op die omeenskakeling tussen kortisol en kortisoon
deur 11βHSD1 and 11βHSD2 in CHO-K1 selle;
• die invloed van Rooibosinname op vlakke van sirkulerende steroïed hormone
en relatiewe verhoudings in die bloed van manlike Wistarrotte;
• die invloed van Rooibosinname op sirkulerende steroïed hormoon vlakke en
relatiewe verhoudings in die bloed van mans en vrouens met ‘n hoë risiko vir
die ontwikkeling van kardiovaskulêre siektes.
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