Mass Spectrometry Letters

Korean Society for Mass Spectrometry (한국질량분석학회)
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In Vitro Inhibitory Effect of Licoricidin on Human Cytochrome P450s

  • Kim, Sunju (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • O, Heungchan (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Kim, Jeong Ah (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Lee, Seung Ho (College of Pharmacy, Yeungnam University) ;
  • Lee, Sangkyu (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2014.07.28
  • Accepted : 2014.08.28
  • Published : 2014.09.30
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Abstract

Licoricidin isolated from Glycyrrhiza uralensis is known to have anticancer, anti-nephritic, anti-Helicobacter pylori, and antibacterial effects. In this study, a cocktail probe assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the modulating effect of licoricidin on cytochrome P450 (CYP) enzymes in human liver microsomes. When licoricidin was incubated at $0-25{\mu}m$ with CYP probes for 60 min at $37^{\circ}C$, it showed potent inhibitory effects on CYP2B6-catalyzed bupropion hydroxylation and CYP2C9-catalyzed diclofenac 4'-hydroxylation with half maximal inhibitory concentration ($IC_{50}$) values of 3.4 and $4.0{\mu}m$, respectively. The inhibition mode of licoricidin was revealed as competitive, dose-dependent, and non-time-dependent, and following the pattern of Lineweaver-Burk plots. The inhibitory effect of licoricidin has been confirmed in human recombinant cDNA-expressed CYP2B6 and 2C9 with $IC_{50}$ values of 4.5 and $0.73{\mu}m$, respectively. In conclusion, this study has shown the potent inhibitory effect of licoricidin on CYP2B6 and CYP2C9 activity could be important for predicting potential herb-drug interactions with substrates that mainly undergo CYP2B- and CYP2C9-mediated metabolism.

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