Two Approaches for Evaluating the Effects of Galangin on the Activities and mRNA Expression of Seven CYP450

Molecules. 2019 Mar 25;24(6):1171. doi: 10.3390/molecules24061171.

Abstract

Galangin is a marker compound of honey and Alpinia officinarum Hance that exhibits great potential for anti-microbial, anti-diabetic, anti-obesity, anti-tumour and anti-inflammatory applications. Galangin is frequently consumed in combination with common clinical drugs. Here, we evaluated the effects of galangin on cytochrome P450 (CYP)-mediated metabolism, using two different approaches, to predict drug⁻drug interactions. Male Sprague Dawley rats were administered galangin daily for 8 weeks. A "cocktail-probes" approach was employed to evaluate the activities of different CYP450 enzymes. Blood samples of seven probe drugs were analysed using liquid chromatography-tandem mass spectrometry in positive and negative electrospray-ionisation modes. Pharmacokinetic parameters were calculated to identify statistical differences. CYP mRNA-expression levels were investigated in real-time quantitative polymerase chain reaction experiments. The galangin-treated group showed significantly decreased AUC0⁻∞ and Cmax values for CYP1A2, and CYP2B3. The galangin-treated group showed significantly increased AUC0⁻∞ and Cmax values for CYP2C13 and CYP3A1. No significant influences were observed in the pharmacokinetic profiles of CYP2C11, CYP2D4 and CYP2E1. The mRNA-expression results were consistent with the pharmacokinetic results. Thus, CYP450 enzyme activities may be altered by long-term galangin administration, suggesting galangin to be a promising candidate molecule for enhancing oral drug bioavailability and chemoprevention and reversing multidrug resistance.

Keywords: CYP450 enzyme; LC-MS/MS; RT-PCR; cocktail probe drug; galangin.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Chromatography, Liquid
  • Cytochrome P-450 Enzyme System / genetics*
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacokinetics
  • Flavonoids / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Liver / metabolism
  • Male
  • Multigene Family
  • RNA, Messenger / genetics*
  • Rats
  • Reproducibility of Results
  • Tandem Mass Spectrometry

Substances

  • Flavonoids
  • RNA, Messenger
  • galangin
  • Cytochrome P-450 Enzyme System