Steviol, an aglycone of steviol glycoside sweeteners, interacts with the pregnane X (PXR) and aryl hydrocarbon (AHR) receptors in detoxification regulation
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28887089
DOI
10.1016/j.fct.2017.09.007
PII: S0278-6915(17)30512-4
Knihovny.cz E-zdroje
- Klíčová slova
- Drug metabolism, Food-drug interactions, Nuclear receptors, Steviol, Stevioside,
- MeSH
- cytochrom P-450 CYP1A2 genetika metabolismus MeSH
- diterpeny kauranové metabolismus MeSH
- hepatocyty metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- metabolická inaktivace MeSH
- pregnanový X receptor MeSH
- receptory aromatických uhlovodíků genetika metabolismus MeSH
- rostlinné extrakty metabolismus MeSH
- senioři MeSH
- sladidla metabolismus MeSH
- steroidní receptory genetika metabolismus MeSH
- Stevia chemie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cytochrom P-450 CYP1A2 MeSH
- diterpeny kauranové MeSH
- pregnanový X receptor MeSH
- receptory aromatických uhlovodíků MeSH
- rostlinné extrakty MeSH
- sladidla MeSH
- steroidní receptory MeSH
- steviol MeSH Prohlížeč
Stevia rebaudiana Bertoni is a herb known for the high content of natural sweeteners in its leaves. Its main secondary metabolite stevioside is used as non-caloric sweetener. No information, however, is available on whether stevioside or steviol interact with drug-metabolizing enzymes and pose the potential risk of food-drug interactions. Similarly, data are lacking on the interactions of steviol and stevioside with key nuclear receptors controlling the expression of the main drug metabolizing enzymes. We studied the interactions of steviol and stevioside with the pregnane X (PXR), vitamin D (VDR), constitutive androstane (CAR), farnesoid X (FXR), glucocorticoid (GR) and aryl hydrocarbon (AHR) receptors, which control expression of genes of xenobiotic metabolism. In addition, the inhibitory activities of steviol and stevioside towards the major cytochrome P450 enzymes CYP3A4, CYP2C9, CYP2D6, CYP1A2 and CYP2B6 were evaluated in vitro. We found that steviol moderately activated the PXR and AHR, resulting in the induction of their target genes including CYP3A4 and CYP1A2 in primary human hepatocytes. A weak inhibition of CYP3A4 and CYP2C9 with steviol was also found. Our results provide mechanistic data indicating that stevioside and stevia sweeteners may have the potential to induce food-drug interactions, a finding that warrants future prospective clinical investigation.
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