Metabolism of chamaechromone in vitro with human liver microsomes and recombinant human drug-metabolizing enzymes

Planta Med. 2014 Apr;80(6):493-7. doi: 10.1055/s-0034-1368302. Epub 2014 Mar 31.

Abstract

Chamaechromone is a major component in the dried roots of Stellera chamaejasme with antihepatitis B virus and insecticidal activity. In this study, metabolic profiles of chamaechromone were investigated in human liver microsomes. One monohydroxide and two monoglucuronides of chamaechromone were identified. The enzyme kinetics for both hydroxylation and glucuronidation were fitted to the Michaelis-Menten equation. The hydroxylation of chamaechromone was inhibited by α-naphthoflavone, and predominantly catalyzed by recombinant human cytochrome P450 1A2, whereas the glucuronidation was inhibited by quercetin, 1-naphthol, and fluconazole, and mainly catalyzed by recombinant human UDP-glucuronosyltransferase 1A3, 1A7, 1A9, and 2B7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / metabolism
  • Benzoflavones / pharmacology
  • Cytochrome P-450 CYP1A2 / metabolism
  • Drug Interactions
  • Drugs, Chinese Herbal / metabolism*
  • Flavones / metabolism*
  • Fluconazole / pharmacology
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Hydroxylation
  • In Vitro Techniques
  • Liver / enzymology
  • Liver / metabolism*
  • Microsomes, Liver / metabolism*
  • Naphthols / pharmacology
  • Plant Roots
  • Quercetin / pharmacology
  • Recombinant Proteins / metabolism
  • Thymelaeaceae / chemistry*

Substances

  • Antiviral Agents
  • Benzoflavones
  • Drugs, Chinese Herbal
  • Flavones
  • Naphthols
  • Recombinant Proteins
  • chamaechromone
  • 1-naphthol
  • alpha-naphthoflavone
  • Fluconazole
  • Quercetin
  • Cytochrome P-450 CYP1A2
  • UDP-glucuronosyltransferase, UGT1A3
  • Glucuronosyltransferase