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<p style="margin-bottom:0cm === margin-bottom:.0001pt === line-height:
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11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">Laboratory studies, epidemiological investigations and human clinical trials indicate</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">that flavonoids have important effects on cancer chemoprevention and therapy.</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">Flavonoids may interfere in several steps that lead to cancer development but may</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">also lead to toxicity as the inhibition of carcinogen-activating enzymes may also cause</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">potential toxic flavonoid-drug interactions. However, the potential toxicity of these</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">dietary components has not been well studied. The use of polyphenol-enriched</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">supplements prepared from South African herbal teas, rooibos (</span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">Aspalathus linearis</span></i><span style="font-size:11.5pt ===
font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">)</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">and honeybush (</span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique ===
mso-bidi-font-family:Helvetica-Oblique">Cyclopia </span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">spp.) are being marketed to alleviate symptoms that are</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">known to be &ldquo === cured&rdquo === by the herbal teas. However, there is a lack of information</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">regarding the possible health promoting effects of these polyphenol-enriched extracts</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">on xenobiotic metabolism. In the present study, the modulating effects of aspalathinenriched</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">rooibos and mangiferin-enriched C. </span><i><span style="font-size:11.5pt === font-family:
Helvetica-Oblique === mso-bidi-font-family:Helvetica-Oblique">genistoides </span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">and </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique ===
mso-bidi-font-family:Helvetica-Oblique">C. subternata </span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">extracts on</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">the gene expression of xenobiotic metabolising enzymes (XMEs) were investigated </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">in</span></i> <i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">vivo </span></i><span style="font-size:11.5pt === font-family:
" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">in the rat liver and kidneys. An </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique ===
mso-bidi-font-family:Helvetica-Oblique">in vitro </span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">study, utilising a primary rat hepatocyte cell</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">model, was included to further evaluate changes in the expression of selected XMEs</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">by the herbal tea extracts, including their major polyphenolic constituents, aspalathin</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">and mangiferin. The use of the </span><i><span style="font-size:11.5pt === font-family:
Helvetica-Oblique === mso-bidi-font-family:Helvetica-Oblique">in vitro </span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">primary hepatocytes assay as a predictive cell</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">model for the modulation of the expression of XMEs genes by the herbal tea extracts</span> <i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">in vivo </span></i><span style="font-size:11.5pt === font-family:
" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">was critically evaluated.</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">In the liver and kidneys, the </span><i><span style="font-size:11.5pt === font-family:
Helvetica-Oblique === mso-bidi-font-family:Helvetica-Oblique">C. subternata </span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">polyphenol-enriched herbal tea extract</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">effected the majority of changes regarding the expression of XMEs genes when</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">compared to the rooibos and </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique ===
mso-bidi-font-family:Helvetica-Oblique">C. genistoides</span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">. Variations in the modulation of gene</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">expression of the XMEs by the herbal tea extracts were related to differences in their</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">polyphenol constituents, although non-polyphenolic constituent could also be involved.</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">Overall the herbal teas regulated alcohol, energy, drug and steroid metabolism in the</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">liver, whereas in the kidneys the gene expression of phase I, phase II, steroid</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">metabolising enzymes, as well as drug transporters were modulated. It would appear</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">that the herbal teas are likely to exhibit both beneficial and adverse effects </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">in vivo</span></i><span style="font-size:11.5pt === font-family:
" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">, depending on the specific organ, the xenobiotic and/or drug that are involved. The</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">primary rat hepatocytes model display varying effects with respect to modulating gene</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">expression of specific XMEs by the polyphenol-enriched herbal tea extracts. Apart</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">from the reduction in 17<span style="font-size:
11.5pt === font-family:TT61t00 === mso-bidi-font-family:TT61t00">&beta === </span>-hydroxysteroid dehydrogenase gene expression care should</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">be taken to directly extrapolate the </span><i><span style="font-size:11.5pt ===
font-family:Helvetica-Oblique === mso-bidi-font-family:Helvetica-Oblique">in vitro </span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">findings to changes that prevail </span><i><span style="font-size:
11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:Helvetica-Oblique">in vivo</span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === ===
mso-bidi-font-family:Helvetica">.</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">However, interesting results regarding the masking effect of complex mixture on the</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">modulation of XME gene expression of individual polyphenols were encountered. In</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">addition differences in the dose and duration of exposure between the </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">in vitro </span></i><span style="font-size:11.5pt ===
font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">and </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">in</span></i> <i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">vivo </span></i><span style="font-size:11.5pt === font-family:
" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">studies were not comparable and should be further explored to validate the </span><i><span style="font-size:11.5pt === font-family:Helvetica-Oblique === mso-bidi-font-family:
Helvetica-Oblique">in vitro</span></i> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">primary hepatocytes model to predict changes </span><i><span style="font-size:11.5pt ===
font-family:Helvetica-Oblique === mso-bidi-font-family:Helvetica-Oblique">in vivo</span></i><span style="font-size:11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:
Helvetica">. Future studies should</span> <span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica">investigate the effects of the herbal tea extracts, its polyphenols and etabolites on</span><span style="font-size:
11.5pt === font-family:" === Helvetica" === ," === sans-serif" === === mso-bidi-font-family:Helvetica"> ME induction at a protein level as well as varying herb-drug-enzyme interactions.</span></p>
<p>  === </p>
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