title: Effects of eleutheroside B and eleutheroside E on activity of cytochrome P450 in rat liver microsomes.
abstract: BACKGROUND
  Chemicals of herbal products may cause unexpected toxicity or adverse effect by the potential for alteration of the activity of CYP450 when co-administered with other drugs. Eleutherococcus senticosus (ES), has been widely used as a traditional herbal medicine and popular herbal dietary supplements, and often co-administered with many other drugs. The main bioactive constituents of ES were considered to be eleutherosides including eleutheroside B (EB) and eleutheroside E (EE). This study was to investigate the effects of EB and EE on CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in rat liver microsomes in vitro.
  
  
  METHODS
  Probe drugs of tolbutamide (TB), dextromethorphan (DM), chlorzoxazone (CLZ) and testosterone (TS) as well as eleutherosides of different concentrations were added to incubation systems of rat liver microsomes in vitro. After incubation, validated HPLC methods were used to quantify relevant metabolites.
  
  
  RESULTS
  The results suggested that EB and EE exhibited weak inhibition against the activity of CYP2C9 and CYP2E1, but no effects on CYP2D6 and CYP3A4 activity. The IC50 values for EB and EE were calculated to be 193.20 μM and 188.36 μM for CYP2E1, 595.66 μM and 261.82 μM for CYP2C9, respectively. Kinetic analysis showed that inhibitions of CYP2E1 by EB and EE were best fit to mixed-type with Ki value of 183.95 μM and 171.63 μM, respectively.
  
  
  CONCLUSIONS
  These results indicate that EB and EE may inhibit the metabolism of drugs metabolized via CYP2C9 and CYP2E1, and have the potential to increase the toxicity of the drugs.
authors.forename: Sixun
authors.initials: S
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Lin
authors.forename: Sheng
authors.initials: S
authors.lastname: Tai
authors.forename: Shuo
authors.initials: S
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. liugaofengwty@126.com.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D002753:Chlorzoxazone / Q000494:pharmacology; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003915:Dextromethorphan / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010666:Phenylpropionates / Q000494:pharmacology*; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D005960:Glucosides; D017705:Lignans; D010666:Phenylpropionates; D013739:Testosterone; D003915:Dextromethorphan; C421885:eleutheroside E; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D065729:Cytochrome P-450 CYP2C9; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone; C028305:syringin