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Rooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes, modulating steroid hormone levels in H295R cells

dc.contributor.authorSchloms, Lindie
dc.contributor.authorSwart, Amanda C.
dc.date.accessioned2014-04-14T09:59:38Z
dc.date.available2014-04-14T09:59:38Z
dc.date.issued2014-03
dc.identifier.citationSchloms, L. & Swart, A. C. 2014. Rooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes, modulating steroid hormone levels in H295R cells. Molecules, 19(3):3681-3695, doi:10.3390/molecules19033681.en_ZA
dc.identifier.issn1420-3049 (print)
dc.identifier.issn1420-3049 (online)
dc.identifier.otherdoi:10.3390/molecules19033681
dc.identifier.urihttp://hdl.handle.net/10019.1/86180
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund.en_ZA
dc.descriptionSchloms, L. & Swart, A. C. 2014. Rooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes, modulating steroid hormone levels in H295R cells. Molecules, 19(3):3681-3695, doi:10.3390/molecules19033681.en_ZA
dc.descriptionThe original publication is available at http://www.mdpi.com/journal/moleculesen_ZA
dc.description.abstractMajor rooibos flavonoids—dihydrochalcones, aspalathin and nothofagin, flavones—orientin and vitexin, and a flavonol, rutin, were investigated to determine their influence on the activity of adrenal steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3βHSD2) and cytochrome P450 (P450) enzymes, P450 17α-hydroxylase/17,20-lyase (CYP17A1), P450 21-hydroxylase (CYP21A2) and P450 11β-hydroxylase (CYP11B1). All the flavonoids inhibited 3βHSD2 and CYP17A1 significantly, while the inhibition of downstream enzymes, CYP21A2 and CYP11B1, was both substrate and flavonoid specific. The ihydrochalcones inhibited the activity of CYP21A2, but not that of CYP11B1. Although rutin, orientin and vitexin inhibited deoxycortisol conversion by CYP11B1 significantly, inhibition of deoxycorticosterone was <20%. These three flavonoids were unable to inhibit CYP21A2, with negligible inhibition of deoxycortisol biosynthesis only. Rooibos inhibited substrate conversion by CYP17A1 and CYP21A2, while the inhibition of other enzyme activities was <20%. In H295R cells, rutin had the greatest inhibitory effect on steroid production upon forskolin stimulation, reducing total steroid output 2.3-fold, while no effect was detected under basal conditions. Nothofagin and vitexin had a greater inhibitory effect on overall steroid production compared to aspalathin and orientin, respectively. The latter compounds contain two hydroxyl groups on the B ring, while nothofagin and vitexin contain a single hydroxyl group. In addition, all of the flavonoids are glycosylated, albeit at different positions—dihydrochalcones at C3' and flavones at C8 on ring A, while rutin, a larger molecule, has a rutinosyl moiety at C3 on ring C. Structural differences regarding the number and position of hydroxyl and glucose moieties as well as structural flexibility could indicate different mechanisms by which these flavonoids influence the activity of adrenal steroidogenic enzymes.en_ZA
dc.description.sponsorshipStellenbosch Universityen_ZA
dc.format.extent15 p.
dc.language.isoen_ZAen_ZA
dc.publisherMDPIen_ZA
dc.subjectAspalathus linearisen_ZA
dc.subjectRooibos polyphenolsen_ZA
dc.subjectSteroid hormonesen_ZA
dc.subjectCytochrome P450 enzymesen_ZA
dc.subjectAdrenocortical hormonesen_ZA
dc.titleRooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes, modulating steroid hormone levels in H295R cellsen_ZA
dc.typeArticleen_ZA
dc.description.versionPublishers' Versionen_ZA
dc.rights.holderAuthors retain copyrighten_ZA


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