An investigation into the stress relieving properties of Sutherlandia frutescens : inhibition of steroidogenic cytochrome P450 enzymes

Prevoo, Desiree (2005-12)

Thesis (MSc)--Stellenbosch University, 2005.

Thesis

ENGLISH ABSTRACT: This study: I. Investigates the influence of S. frutescens on the binding properties of cytochrome P450-dependent enzymes in ovine adrenocortical mitochondria and microsomes, demonstrating that S. frutescens extracts elicit difference spectra and inhibit the Type 1 difference spectra induced by natural steroids. II. Indicates inhibition by S. frutescens extracts of the catalytic activity of cytochrome P450-dependent-17a-hydroylase and cytochrome P450-dependentsteroid- 21-hydroxylase enzymes in ovine adrenocortical microsomes. III. Describes an assay determining the inhibitory effects of S. frutescens, in COS L cells, on individual cytochrome P450-dependent enzymes - ovine, baboon and human cytochrome P450-dependent- L7a-hydroylase, and bovine cytochrome P450-dependent-21-hydroxylase enzymes. IV. Demonstrates that the inhibition of elevated plasma glucocorticoid levels in rats exposed to chronic immobilization stress could possibly be attributed to the influence of hydrophilic and hydrophobic compounds in S. frutescens on cytochromes P450-depndent enzymes.

AFRIKAANSE OPSOMMING: Hierdie studie: I. Ondersoek die invloed van S. frutescens op die bindingseienskappe van sitochroom P450-afhanklike ensieme in skaapbynier mitokondriale en - mikrosomale preparate en toon aan dat komponente in S. frutescens ekstrakte verskil spektra induseer en tipe I verskil spektra van natuurlike steroïede inhibeer. II. Dui die inhiberende effek van S. frutescens ekstrakte op die katalitiese aktiwiteit van sitochroom P450-afhanklike-17a-hidroksilase en sitochroom P450- afhanklike-steroïed- 21-hidroksilase ensieme in skaapbyniermikrosome aan. III. Beskryf 'n tegniek om die inhiberende effek van S. frutescens op individuele sitochroom P450-afhankilike ensieme - bobbejaan, skaap en mens sitochroom P450-afhanklike-17a-hidroksilase, en bees sitochroom P450-afhanklike-steroïed- 21-hidroksilase - in COS 1 selle te bepaal. IV. Demonstreer dat inhibisie van verhoogde glukokortikoïed plasma konsentrasies waargeneem in rotte blootgestel aan kroniese immobiliserende stress, moontlik toegeskryf kan word aan die effek van S. frutescens op die sitochroom P450- afhanklike ensieme.

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