title: Effect of an ethanol extract of Descurainia sophia seeds on Phase I and II drug metabolizing enzymes and P-glycoprotein activity in vitro.
abstract: BACKGROUND
  Descurainia sophia seeds have a variety of pharmacological functions and been widely used in traditional folk medicine. However, their effects on human drug metabolizing enzyme (DME) activities have not been elucidated. The present study investigated the inhibitory effects of an ethanol extract of D. sophia seeds (EEDS) on human Phase I/II (DMEs) and P-glycoprotein (p-gp) in vitro.
  
  
  METHODS
  The enzyme activities of human Phase I (cytochrome P450s, CYPs), Phase II (uridine diphosphate glucuronosyltransferases, UGTs) DMEs, and the drug transporter P-gp were determined in the presence of various concentrations of EEDS using commercially available luminogenic assay systems. The mode of enzyme inhibition and the inhibitory constant (Ki) value of EEDS were graphically determined with Lineweaver-Burk double reciprocal plots and secondary plots, respectively.
  
  
  RESULTS
  The enzyme activity assays showed that EEDS moderately inhibited the CYP1A2, CYP2C9, and CYP2C19 isoforms with half maximal inhibitory concentrations (IC50) of 47.3, 25.8, and 38.7 μg/mL, respectively. Graphical analyses with Lineweaver-Burk double reciprocal plots and secondary plots indicated that EEDS competitively inhibited CYP2C9 with a Ki value of 19.8 μg/mL; however, it inhibited CYP2C9 and CYP2C19 in a mixed mode with Ki values of 5.2, and 11.9 μg/mL, respectively. Other Phase I (CYP2C8, CYP2D6, and CYP3A4) and Phase II (UGT1A1 and UGT2B7) enzymes as well as P-gp were weakly or negligibly affected by EEDS with concentrations up to 500 μg/mL.
  
  
  CONCLUSIONS
  EEDS is a selective inhibitor of CYP1A2, CYP2C9, and CYP2C19 with moderate enzymatic inhibition. Clinically, full consideration should be given to a potential toxic adverse effect from a herb-drug interaction when drugs that are particularly susceptible to CYP1A2, CYP2C9, or CYP2C19-mediated metabolism are taken together with EEDS. Characterization of metabolic profiles of specific herbal drugs could help consumers and medical specialists to use them safely as a complementary and alternative medicine.
authors.affiliation: KM-Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea. jmyi@kiom.re.kr.
authors.forename: Jin-Mu
authors.initials: JM
authors.lastname: Yi
authors.affiliation: KM-Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea. kya8525@kiom.re.kr.
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Kim
authors.affiliation: KM-Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea. ojung8384@kiom.re.kr.
authors.forename: You Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: KM-Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea. osbang@kiom.re.kr.
authors.forename: Ok-Sun
authors.initials: OS
authors.lastname: Bang
authors.affiliation: KM-Convergence Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea. nosookim@kiom.re.kr.|Department of Korean Medicine, Life Science and Technology, Korea University of Science and Technology, Daejeon, Republic of Korea. nosookim@kiom.re.kr.
authors.forename: No Soo
authors.initials: NS
authors.lastname: Kim
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry / Q000378:metabolism; D019607:Brassicaceae / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D014453:Glucuronosyltransferase / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D050216:Metabolic Detoxication, Phase I; D050217:Metabolic Detoxication, Phase II; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification; D012639:Seeds / Q000737:chemistry
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase