title: Two potent cytochrome P450 2D6 inhibitors found in Rhodiola rosea.
abstract: OBJECTIVE
  Throughout the world, in particular in Russia, Northern Europe and China, Rhodiola species are used as herb supplements. Previously, we found that the extract of Rhodiola rosea, one of the most widely used Rhodiola species, had an inhibitory effect on the catalytic activity of cytochrome P450 2D6. Here, its inhibitory components were identified.
  
  
  METHODS
  A human liver microsomal in vitro system was used with dextromethorphan as substrate. The production rate of destrorphan, a metabolite of dextromethorphan, was used to measure enzyme activity. The concentration of destrorphan in the samples was measured using LC-MS/MS. Inhibitory activity of eight main components from Rhodiola rosea was evaluated.
  
  
  RESULTS
  Rhodiosin and rhodionin showed inhibitory activity with IC50 values of 0.761 microM and 0.420 microM, respectively. The other components showed no obvious inhibition (with a residual enzyme activity of more than 90%). Both rhodiosin and rhodionin were determined to be non-competitive inhibitors with Ki values of 0.769 microM and 0.535 microM.
  
  
  CONCLUSIONS
  Two of the main Rhodiola rosea compounds, rhodiosin and rhodionin, can inhibit cytochrome P450 2D6 non-competitively with high specificity which could have implications for interactions with co-administered drugs.
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University Medical College, Qingdao, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Qingdao University Medical College, Qingdao, P. R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University Medical College, Qingdao, P. R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University Medical College, Qingdao, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University Medical College, Qingdao, P. R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University Medical College, Qingdao, P. R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University Medical College, Qingdao, P. R. China.
authors.forename: Zhongguo
authors.initials: Z
authors.lastname: Sui
mesh_terms: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009005:Monosaccharides / Q000494:pharmacology*; D010090:Oxidoreductases, O-Demethylating / Q000378:metabolism; D029771:Rhodiola / Q000737:chemistry*
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007202:Indicators and Reagents; D009005:Monosaccharides; C530045:rhodionin; D003577:Cytochrome P-450 Enzyme System; C534195:rhodiosin; D010090:Oxidoreductases, O-Demethylating; C052861:dextromethorphan O-demethylase