The influence of Aspalathus linearis flavonoids on glucocorticoid biosynthesis

Abstract

Flavonoids exhibit a wide range of biological activities, including the modulation of adrenal steroidogenic enzymes, thus influencing steroidogenesis. Aspalathus linearis (Rooibos), a dietary source rich in flavonoids, was investigated to determine the influ-ence on glucocorticoid biosynthesis. The influence of Rooibos on P450 17a-hydroxylase (CYP17),P450 21-hydroxylase (CYP21), P450 11b-hydroxylase (CYP11B1)and 3b-hydroxysteroid dehydrogenase II (3bHSD) was determined in COS1 cells. The outcome of steroid metabolism was also determined in H295R cells in the presence of Rooibos. Plasma cortisol (F) levels were investigated in human subjects consuming Rooibos and in Wistar rats to determine the influenceof Rooibos on corticosterone (CORT) production. The inhibition of CYP17, CYP21 and 3bHSD was significant(p < 0.001) while the inhibition of CYP11B1 was negligible.Aspalathin, a flavonoid compound unique to Rooibos, inhibitedCYP21 and 3bHSD (p < 0.001) significantly with markedly lessinhibition of CYP17. In H295R cells, pregnenolone metabolismwas inhibited by Rooibos (p < 0.001) while aspalathin inhibitedCORT (p < 0.05) and deoxycortisol (S) and increased andro-stenedione production. In vivo studies showed male serum F lev-els remaining unchanged together with increased testosterone levels while females showed a downward trend in F levels and increased dehydroepiandrostenedione sulphate levels. CORT concentrations in rats receiving Rooibos were significantly decreased(p < 0.05). Both studies showed in the inactivation of the respective glucocorticoids to be increased, resulting in a marked decrease in the CORT:11-dehydroCORT and F:cortisone (E)ratios. Rooibos influences the flux within the adrenal steroidogenic path-ways and the outcome of steroidogenesis. Preliminary investigations into the interconversion of F and E showed that Rooibos favours the production of the inactive metabolite, indicating possible clinical applications in hypertension and metabolic syndrome.