Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer-binding protein beta activation

Title
Capsaicin induces CYP3A4 expression via pregnane X receptor and CCAAT/enhancer-binding protein beta activation
Author(s)
한은희[한은희]김형균[김형균]최재호[최재호]장인진[장인진]이상섭[이상섭]권광일[권광일]김은영[김은영]노금한[노금한]정태천황용필[황용필]정용철[정용철]강원구정혜광[정혜광]
Keywords
NUCLEAR RECEPTOR; TRANSCRIPTION FACTORS; MOLECULAR-MECHANISM; SIGNALING PATHWAY; INDUCED APOPTOSIS; HEPG2 CELLS; PAIN; ANTAGONIST; METABOLISM; INDUCTION
Issue Date
201205
Publisher
WILEY-BLACKWELL
Citation
MOLECULAR NUTRITION & FOOD RESEARCH, v.56, no.5, pp.797 - 809
Abstract
Scope Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the principal pungent ingredient in hot red and chili peppers. Many studies have focused on the anticarcinogenic or chemopreventive activities of capsaicin. However, the influence of capsaicin on CYP3A4, its involvement in drug metabolism, and the underlying mechanisms remain unclear. Methods and results Here, we examined the effect of capsaicin on CYP3A4 expression and the metabolism of CYP3A1 substrate, nifedipine in male SpragueDawley rats. Capsaicin induced the enzymatic activity and expression of CYP3A4 in HepG2 cells. Treatment with a human pregnane X receptor (hPXR) inhibitor reduced the inductive effects of capsaicin on CYP3A4 expression. Capsaicin also induced the activation of CCAAT/enhancer-binding protein beta (C/EBP beta). Moreover, capsaicin increased the activation of the transient receptor potential vanilloid type-1 receptor downstream signaling components Ca2+/calmodulin-dependent protein kinase and Akt. Capsaicin elevated the level of CYP3A1 in rat liver and significantly increased the biotransformation of nifedipine to dehydronifedipine. Conclusion From these data, we conclude that capsaicin induces CYP3A4 expression in vitro and in vivo. This induction was achieved by the activation of hPXR and C/EBP beta. Our results suggest that capsaicin might induce CYP3A4 expression; thus, exposure to capsaicin may increase the metabolism of CYP3A4 substrate and potentially cause fooddrug interactions.
URI
http://hdl.handle.net/YU.REPOSITORY/28385http://dx.doi.org/10.1002/mnfr.201100697
ISSN
1613-4125
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약학대학 > 약학부 > Articles
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