Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Inhibition of Cytochrome P450 by Propolis in Human Liver Microsomes

  • Ryu, Chang Seon (College of Pharmacy, Chungnam National University) ;
  • Oh, Soo Jin (Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Jung Min (College of Pharmacy, Chungnam National University) ;
  • Lee, Ji-Yoon (College of Pharmacy, Chungnam National University) ;
  • Lee, Sang Yoon (College of Pharmacy, Chungnam National University) ;
  • Chae, Jung-woo (College of Pharmacy, Chungnam National University) ;
  • Kwon, Kwang-il (College of Pharmacy, Chungnam National University) ;
  • Kim, Sang Kyum (College of Pharmacy, Chungnam National University)
  • Received : 2016.04.15
  • Accepted : 2016.05.23
  • Published : 2016.07.15
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Abstract

Although propolis is one of the most popular functional foods for human health, there have been no comprehensive studies of herb-drug interactions through cytochrome P450 (CYP) inhibition. The purpose of this study was to determine the inhibitory effects of propolis on the activities of CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 using pooled human liver microsomes (HLMs). Propolis inhibited CYP1A2, CYP2E1 and CYP2C19 with an $IC_{50}$ value of 6.9, 16.8, and $43.1{\mu}g/mL$, respectively, whereas CYP2A6, 2B6, 2C9, 2D6, and 3A4 were unaffected. Based on half-maximal inhibitory concentration shifts between microsomes incubated with and without nicotinamide adenine dinucleotide phosphate, propolis-induced CYP1A2, CYP2C19, and CYP2E1 inhibition was metabolism-independent. To evaluate the interaction potential between propolis and therapeutic drugs, the effects of propolis on metabolism of duloxetine, a serotonin-norepinephrine reuptake inhibitor, were determined in HLMs. CYP1A2 and CYP2D6 are involved in hydroxylation of duloxetine to 4-hydroxy duloxetine, the major metabolite, which was decreased following propolis addition in HLMs. These results raise the possibility of interactions between propolis and therapeutic drugs metabolized by CYP1A2.

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References

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