Ephedra water decoction and cough tablets containing ephedra and liquorice induce CYP1A2 but not CYP2E1 hepatic enzymes in rats

Xenobiotica. 2016;46(2):141-6. doi: 10.3109/00498254.2015.1060371. Epub 2015 Jul 7.

Abstract

1. Ephedra water decoction (EWD) and cough tablets containing ephedra and liquorice (maxing cough tablets, MXCT) have been widely used in the treatment of asthma. In the clinic, EWD and MXCT may be prescribed with theophylline, one of the most popular antiasthmatic drugs. CYP1A2 and CYP2E1 are mainly involved in the oxidative metabolism of theophylline in human liver. Drug interactions involving the cytochrome P450 (CYP) isoforms generally are of two types: enzyme induction or enzyme inhibition. Enzyme inhibition reduces metabolism, whereas induction can increase it. 2. To evaluate the pretreatment effect of EWD and MXCT on CYP1A2 and CYP2E1, CYP1A2 and CYP2E1 activity, the protein expression and mRNA expression levels were determined. After pretreatment with EWD or MXCT, the enzyme activity, mRNA expression and protein expression of CYP1A2 were increased significantly (p < 0.05), but enzyme activity of CYP2E1 did not change compared with the control. 3. It was demonstrated that EWD or MXCT pretreatment obviously induced CYP1A2, therefore, in patients taking EWD or MXCT, possible CYP-induced drug interaction should be noted to decrease the risk of therapeutic failure or adverse effects resulting from the use of additional therapeutic agents.

Keywords: CYP1A2; CYP2E1; drug–drug interaction; ephedra water decoction; maxing cough tablets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Asthmatic Agents / pharmacology
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2E1 / metabolism*
  • Cytochromes / metabolism*
  • Ephedra / chemistry*
  • Glycyrrhiza / chemistry*
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Plant Preparations / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Tablets
  • Theophylline / pharmacology

Substances

  • Anti-Asthmatic Agents
  • Cytochromes
  • Plant Preparations
  • RNA, Messenger
  • Tablets
  • Theophylline
  • Cytochrome P-450 CYP2E1
  • Cyp1a2 protein, rat
  • Cytochrome P-450 CYP1A2