Influence of Ginsenoside Rh 1 and F 1 on Human Cytochrome P450 Enzymes

Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, 457 Zhong-shan Road, Dalian 116023, P. R. China.
Planta Medica (Impact Factor: 2.15). 03/2006; 72(2):126-31. DOI: 10.1055/s-2005-873197
Source: PubMed


For an oral herbal medicine, the components that can enter the systemic circulation may be the really effective components. In the present study, the effects on the human cytochrome P450 activities of ginsenoside Rb (1) and two hydrolysis products of 20( S)-protopanaxatriol ginsenosides in humans, namely ginsenoside Rh (1) and F (1), which may reach the systemic circulation after oral administration of ginseng extract, were evaluated. Our results showed that Rb (1) exhibited no marked effects on the activities of human cytochrome P450, whereas Rh (1) and F (1) exhibited competitive inhibition of the activity of CYP3A4 with K(i) values of 57.7 +/- 9.6 microM and 67.8 +/- 16.2 microM, respectively. F (1) also exhibited a weaker inhibition of the activity of CYP2D6. Rh (1) exhibited a weak stimulation rather than an inhibition of the activity of CYP2E1. The degradation of ginsenosides in the gastrointestinal tract may play an important role in the ginseng-associated drug-drug interactions, but the effects might be not due to Rh (1) and F (1).

Download full-text


Available from: Yong Liu
  • Source
    • "Increasing attention has been paid to the role of herb metabolites in herb-drug interactions [15] [16] [17] [18] [19]. Previous study showed that icariin could be metabolized to three main metabolites icariside I, icariside II, and icaritin by the bacteria in rat intestine (Figure 1). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Icariin is known as an indicative constituent of the Epimedium genus, which has been commonly used in Chinese herbal medicine to enhance treat impotence and improve sexual function, as well as for several other indications for over 2000 years. In this study, we aimed to investigate the effects of icariin and its intestinal metabolites on the activities of human UDP-glucuronosyltransferase (UGT) activities. Using a panel of recombinant human UGT isoforms, we found that icariin exhibited potent inhibition against UGT1A3. It is interesting that the intestinal metabolites of icariin exhibited a different inhibition profile compared with icariin. Different from icariin, icariside II was a potent inhibitor of UGT1A4, UGT1A7, UGT1A9, and UGT2B7, and icaritin was a potent inhibitor of UGT1A7 and UGT1A9. The potential for drug interactions in vivo was also quantitatively predicted and compared. The quantitative prediction of risks indicated that in vivo inhibition against intestinal UGT1A3, UGT1A4, and UGT1A7 would likely occur after oral administration of icariin products.
    Full-text · Article · Oct 2012 · Evidence-based Complementary and Alternative Medicine
  • Source
    • "The mixture was centrifuged at 20 000×g for 10 min, and an aliquot of supernatant was then transferred to a 0.3-mL auto-injector vial for HPLC or UFLC analysis. The incubation conditions, including substrate and protein concentrations and incubation times, have been reported21, 22. The HPLC system (SHIMADZU, Kyoto, Japan) consisted of a SCL-10A system controller, two LC-10AT pumps, a SIL-10A autoinjector, and a SPD-10AVP UV detector or a RF-10AXL fluorescence detector. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To ascertain the effects of erlotinib on CYP3A, to investigate the amplitude and kinetics of erlotinib-mediated inhibition of seven major CYP isoforms in human liver microsomes (HLMs) for evaluating the magnitude of erlotinib in drug-drug interaction in vivo. The activities of 7 major CYP isoforms (CYP1A2, CYP2A6, CYP3A, CYP2C9, CYP2D6, CYP2C8, and CYP2E1) were assessed in HLMs using HPLC or UFLC analysis. A two-step incubation method was used to examine the time-dependent inhibition of erlotinib on CYP3A. The activity of CYP2C8 was inhibited with an IC(50) value of 6.17±2.0 μmol/L. Erlotinib stimulated the midazolam 1'-hydroxy reaction, but inhibited the formation of 6β-hydroxytestosterone and oxidized nifedipine. Inhibition of CYP3A by erlotinib was substrate-dependent: the IC(50) values for inhibiting testosterone 6β-hydroxylation and nifedipine metabolism were 31.3±8.0 and 20.5±5.3 μmol/L, respectively. Erlotinib also exhibited the time-dependent inhibition on CYP3A, regardless of the probe substrate used: the value of K(I) and k(inact) were 6.3 μmol/L and 0.035 min(-1) for midazolam; 9.0 μmol/L and 0.045 min(-1) for testosterone; and 10.1 μmol/L and 0.058 min(-1) for nifedipine. The inhibition of CYP3A by erlotinib was substrate-dependent, while its time-dependent inhibition on CYP3A was substrate-independent. The time-dependent inhibition of CYP3A may be a possible cause of drug-drug interaction, suggesting that attention should be paid to the evaluation of erlotinib's safety, especially in the context of combination therapy.
    Full-text · Article · Mar 2011 · Acta Pharmacologica Sinica
  • Source
    • "The chemical inhibition assay was carried out as previously reported ( Liu et al . 2006a ; Zhang et al . 2007 ) . A typical incubation mixture contained 0 . 5 mg protein ml À1 HLM or RLM , an NADPH - generating system , 50 mM triptolide and selective inhibitors of each human CYP isoform in a 100 mM phosphate buffer ( pH 7 . 4 ) . The inhibitors used were as follows : furafylline ( 10 mM ) for CYP1A2 , 8"
    [Show abstract] [Hide abstract]
    ABSTRACT: Triptolide, the primary active component of a traditional Chinese medicine Tripterygium wilfordii Hook F, has a wide range of pharmacological activities. In the present study, the metabolism of triptolide by cytochrome P450s was investigated in human and rat liver microsomes. Triptolide was converted to four metabolites (M-1, M-2, M-3, and M-4) in rat liver microsomes and three (M-2, M-3, and M-4) in human liver microsomes. All the products were identified as mono-hydroxylated triptolides by liquid chromatography-mass spectrometry (LC-MS). The studies with chemical selective inhibitors, complementary DNA-expressed human cytochrome P450s, correlation analysis, and enzyme kinetics were also conducted. The results demonstrate that CYP3A4 and CYP2C19 could be involved in the metabolism of triptolide in human liver, and that CYP3A4 was the primary isoform responsible for its hydroxylation.
    Full-text · Article · Jan 2009 · Xenobiotica
Show more