Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes

Yong Liu, Jiang Wei Zhang, Wei Li, Hong Ma, Jie Sun, Mai Cun Deng, Ling Yang

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

There is still an argument about ginseng-prescription drug interactions. To evaluate the influence on cytochrome P450 (P450) activities of ginseng in the present study, the influence on P450 activities of naturally occurring ginsenosides and their degradation products in human gut lumen was assayed by using human liver microsomes and cDNA-expressed CYP3A4. The results showed that the naturally occurring ginsenosides exhibited no inhibition or weak inhibition against human CYP3A4, CYP2D6, CYP2C9, CYP2A6, or CYP1A2 activities; however, their main intestinal metabolites demonstrated a wide range of inhibition of the P450-mediated metabolism. There was no mechanism-based inhibition found on these P450 isoforms. It is noteworthy that Compound K, protopanaxadiol (Ppd), and protopanaxatriol (Ppt) all exhibited moderate inhibition against CYP2C9 activity, and Ppd and Ppt also exhibited potent competitive inhibition against CYP3A4 activity. We suggest that after oral administration, naturally occurring ginsenosides might influence hepatic P450 activity in vivo via their intestinal metabolites.

Original languageEnglish (US)
Pages (from-to)356-364
Number of pages9
JournalToxicological Sciences
Volume91
Issue number2
DOIs
StatePublished - Jun 1 2006

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Ginsenosides
Cytochrome P-450 CYP3A
Metabolites
Cytochrome P-450 Enzyme System
Enzyme inhibition
Panax
Drug interactions
Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP2D6
Prescription Drugs
Liver Microsomes
Drug Interactions
Metabolism
Liver
Oral Administration
Protein Isoforms
Complementary DNA
Degradation
protopanaxadiol
protopanaxatriol

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. / Liu, Yong; Zhang, Jiang Wei; Li, Wei; Ma, Hong; Sun, Jie; Deng, Mai Cun; Yang, Ling.

In: Toxicological Sciences, Vol. 91, No. 2, 01.06.2006, p. 356-364.

Research output: Contribution to journalArticle

Liu, Yong ; Zhang, Jiang Wei ; Li, Wei ; Ma, Hong ; Sun, Jie ; Deng, Mai Cun ; Yang, Ling. / Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. In: Toxicological Sciences. 2006 ; Vol. 91, No. 2. pp. 356-364.
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