Journal
NUTRIENTS
Volume 13, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/nu13051709
Keywords
pregnane X receptor; vitamin K; isoprenoids; drug-nutrient interaction
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [23380070, 17H0314, 20H02928]
- JSPS
- Grants-in-Aid for Scientific Research [20H02928, 23380070] Funding Source: KAKEN
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PXR acts as a key regulator of defense against foreign substances and can be activated by dietary supplements, impacting drug metabolism efficiency through interactions with drugs and nutrients.
The pregnane X receptor (PXR) is the key regulator of our defense mechanism against foreign substances such as drugs, dietary nutrients, or environmental pollutants. Because of increased health consciousness, the use of dietary supplements has gradually increased, and most of them can activate PXR. Therefore, an analysis of the interaction between drugs and nutrients is important because altered levels of drug-metabolizing enzymes or transporters can remarkably affect the efficiency of a co-administered drug. In the present study, we analyzed the effect of vitamin K-mediated PXR activation on drug metabolism-related gene expression in intestine-derived LS180 cells via gene expression studies and western blotting analyses. We demonstrated that menaquinone 4 (MK-4), along with other vitamin Ks, including vitamin K-1, has the potential to induce MDR1 and CYP3A4 gene expression. We showed that PXR knockdown reversed MK-4-mediated stimulation of these genes, indicating the involvement of PXR in this effect. In addition, we showed that the expression of MDR1 and CYP3A4 genes increased synergistically after 24 h of rifampicin and MK-4 co-treatment. Our study thus elucidates the importance of drug-nutrient interaction mediated via PXR.
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