The inhibitory effects of herbal components on CYP2C9 and CYP3A4 catalytic activities in human liver microsomes

Am J Ther. May-Jun 2004;11(3):206-12. doi: 10.1097/00045391-200405000-00009.

Abstract

Herbal medicines are widely consumed by patients in different clinical settings in the United States and all over the world. In this study, 7 herbal components ginsenosides Rb1, Rb2, Rc, and Rd (from ginseng quercetin) ginkgolides A and B (from ginkgo biloba) were investigated for their inhibitory effects on hepatic CYP2C9 and CYP3A4 catalytic activities in human liver microsomes. Tolbutamide 4-methylhydroxylation and testosterone 6beta-hydroxylation were used as index reactions of CYP2C9 or CYP3A4 catalytic activities, respectively. The metabolites of both reactions were measured by high-performance liquid chromatography and used as indicators of whether enzymes were inhibited or unaffected by these agents. Herbal components were studied at various concentrations (0.1, 1, 10, 100, 200 micromol/L). The herbal compounds investigated were capable of inhibiting CYP2C9 and CYP3A4 catalytic activities, but the potencies differed. Quercetin showed marked inhibitory effects on both tolbutamide 4-methylhydroxylation and testosterone 6beta-hydroxylation with IC(50) values of 35 and 38 micromol/L, respectively. Ginsenoside Rd also had significant inhibitory potency on both CYP2C9- and CYP3A4-mediated index reactions with IC(50) values of 105 and 62 micromol/L, respectively. Ginsenosides Rb1, Rb2, and Rc had limited inhibitory activities on both enzyme reaction systems, whereas the effects of ginkgolides A and B appeared negligible. It is concluded that the components of ginseng and ginkgo biloba screened are capable of inhibiting CYP2C9- and CYP3A4-mediated metabolic reactions. Our findings suggest that quercetin and ginsenoside Rd have the potential to interact with conventional medicines that are metabolized by CYP2C9 and CYP3A4 in vivo.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / drug effects*
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Ginkgo biloba*
  • Ginsenosides / pharmacology*
  • Humans
  • Hydroxylation / drug effects
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / metabolism
  • Plant Extracts / pharmacology*
  • Testosterone / metabolism
  • Tolbutamide / metabolism

Substances

  • Enzyme Inhibitors
  • Ginsenosides
  • Plant Extracts
  • Testosterone
  • Cytochrome P-450 Enzyme System
  • Tolbutamide
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human