Gene expression of xenobiotic metabolising enzymes in rat liver and kidney: differential effects of rooibos and honeybush herbal teas
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Laboratory studies, epidemiological investigations and human clinical trials indicate that flavonoids have important effects on cancer chemoprevention and therapy. Flavonoids may interfere in several steps that lead to cancer development but may also lead to toxicity as the inhibition of carcinogen-activating enzymes may also cause potential toxic flavonoid-drug interactions. However, the potential toxicity of these dietary components has not been well studied. The use of polyphenol enriched supplements prepared from South African herbal teas, rooibos(Aspalathus linearis)and honeybush (Cyclopia spp.) are being marketed to alleviate symptoms that are known to be “cured” by the herbal teas. However, there is a lack of information regarding the possible health promoting effects of these polyphenol-enriched extracts on xenobiotic metabolism. In the present study, the modulating effects of aspalathinenriched rooibos and mangiferin-enriched C. genistoides and C. subternata extracts on the gene expression of xenobiotic metabolising enzymes (XMEs) were investigated in vivo in the rat liver and kidneys. An in vitro study, utilising a primary rat hepatocyte cell model, was included to further evaluate changes in the expression of selected XMEs by the herbal tea extracts, including their major polyphenolic constituents, aspalathin and mangiferin. The use of the in vitro primary hepatocytes assay as a predictive cell model for the modulation of the expression of XMEs genes by the herbal tea extracts in vivo was critically evaluated.In the liver and kidneys, the C. subternata polyphenol-enriched herbal tea extract effected the majority of changes regarding the expression of XMEs genes when compared to the rooibos and C. genistoides. Variations in the modulation of gene expression of the XMEs by the herbal tea extracts were related to differences in their polyphenol constituents, although non-polyphenolic constituent could also be involved.Overall the herbal teas regulated alcohol,energy, drug and steroid metabolism in the liver, whereas in the kidneys the gene expression of phase I, phase II, steroid metabolising enzymes, as well as drug transporters were modulated. It would appear that the herbal teas are likely to exhibit both beneficial and adverse effects in vivo,depending on the specific organ, the xenobiotic and/or drug that are involved. The primary rat hepatocytes model display varying effects with respect to modulating gene expression of specific XMEs by the polyphenol-enriched herbal tea extracts. Apart from the reduction in 17 -hydroxysteroid dehydrogenase gene expression care should be taken to directly extrapolate the in vitro findings to changes that prevail in vivo.However, interesting results regarding the masking effect of complex mixture on the modulation of XME gene expression of individual polyphenols were encountered. In addition differences in the dose and duration of exposure between the in vitro and in vivo studies were not comparable and should be further explored to validate the in vitro primary hepatocytes model to predict changes in vivo. Future studies should investigate the effects of the herbal tea extracts, its polyphenols and metabolites on XME induction at a protein level as well as varying herb-drug-enzyme interactions.