Abstract
Peony (Paeonia lactiflora Pall-) is a plant medicine and a functional food ingredient with wide application for more than 2000 years. It can be coadministrated with many other drugs, composed of traditional Chinese medicine compound such as shaoyao-gancao decoction. In order to explore the efficacy and safety of peony, effects of paeoniflorin and albiflorin (the principal components of peony) on cytochrome P450 (CYP) 3A4 and CYP2D6 were analyzed in human hepatoma HepG2 cells and evaluated from the level of recombinant CYP enzymes in vitro. The findings indicated that albiflorin possessed stronger regulation on the mRNA expression of CYP3A4 and CYP2D6 than paeoniflorin. For the protein level of CYP3A4, albiflorin showed significant induction or inhibition with the concentration increasing from 10−7 M to 10−5 M, but no remarkable variation was observed in paeoniflorin-treated group. Enzyme activity assay implied that both paeoniflorin and albiflorin could regulate CYP3A4 and CYP2D6 with varying degrees. The results showed that albiflorin should be given more attention because it may play a vital role on the overall efficacy of peony. The whole behavior of both paeoniflorin and albiflorin should be focused on ensuring the rationality and effectiveness of clinical application.
Highlights
The cytochrome P450 (CYP) enzymes, acting as important metabolic enzymes in humans, are involved in a diverse array of physiological and xenobiotic metabolic pathways
Cytotoxicity of paeoniflorin and albiflorin on HepG2 cells was detected with MTT assay
We evaluated the regulation of paeoniflorin and albiflorin on CYP3A4 and CYP2D6 from different perspectives, including mRNA expression, protein expression, and enzyme activity
Summary
The cytochrome P450 (CYP) enzymes, acting as important metabolic enzymes in humans, are involved in a diverse array of physiological and xenobiotic metabolic pathways. Modulation of CYP450 isoenzymes via inhibition or induction may evoke severe adverse effects such as decreasing the bioavailability of drugs and inducing toxic reaction [1, 2]. The major isoenzymes of human CYP450 isoenzymes mainly consist of CYP3A4, CYP2D6, CYP1A2, CYP2C9, and CYP2C19, and they metabolize approximately 90% of the known drugs in vivo [3]. Drug combination is associated with the alteration of CYP450 metabolism, including inhibition (resulting in treatment failures) and induction (leading to toxicity) [5, 6]. The investigation of herbs or drugs on CYP450 isoenzymes is critical for guiding drug applications. It could provide bases for researching the lead compounds and guiding the use of combination drug therapy in clinic as well
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