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Ginkgo biloba extract potentiates human vitamin D receptor‐mediated increase in CYP2B6 reporter activity by 1α,25‐dihydroxyvitamin D 3 (1141.8)
Author(s) -
Lau Aik Jiang,
Chang Thomas
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1141.8
Subject(s) - calcitriol receptor , ginkgo biloba , pharmacology , chemistry , pregnane x receptor , reporter gene , cyp2b6 , transfection , constitutive androstane receptor , receptor , biochemistry , nuclear receptor , biology , in vitro , gene expression , gene , microsome , cyp1a2 , transcription factor
Vitamin D receptor (VDR) regulates the expression of a broad array of genes, including those involved in drug biotransformation (e.g. CYP2B6). Ginkgo biloba extract induces CYP2B6, but it is not known whether it activates VDR. Therefore, we characterized the effect of G. biloba extract on human VDR (hVDR) activity. As assessed in a cell‐based dual‐luciferase reporter gene assay, G. biloba extract did not activate hVDR in cells transfected with a hVDR expression plasmid and a CYP2B6‐PBREM/XREM reporter plasmid. In contrast, 1α,25‐dihydroxyvitamin D 3 , which is a hVDR agonist, increased it by 16‐fold compared to the vehicle‐treated group. The combination of G. biloba extract and 1α,25‐dihydroxyvitamin D 3 further increased hVDR activity by another 14‐fold (i.e. 225‐fold increase compared to the vehicle‐treated group). This potentiation effect was evident in multiple lots of G. biloba extract and with other VDR agonists (i.e. lithocholic acid and 9‐cis retinoic acid), and it increased as the concentration of the extract or 1α,25‐dihydroxyvitamin D 3 increased. In contrast, the potentiation did not occur when cells were transfected with a plasmid expressing human constitutive androstane receptor, human pregnane X receptor, or mouse VDR. Overall, the findings indicate that G. biloba extract potentiates hVDR‐mediated CYP2B6 reporter activity. Grant Funding Source : Supported by the Canadian Institutes of Health Research and Michael Smith Fdn. for Health Res.