title: Inhibition of human liver cytochrome P450 by star fruit juice.
abstract: OBJECTIVE
  To examine the inhibitory effects of star fruit (Averrhoa carambola) juice towards seven major cytochrome P450 (CYP) isoforms and NADPH-cytochrome P450 reductase (CPR).
  
  
  METHODS
  The inhibitory effects of star fruit juice (0.5 to 5%, v/v) against the activities of seven CYP isoforms including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP3A4 and CPR were examined in human liver microsomes. To identify time-dependent inhibition, star fruit juice (2.5%, v/v) was preincubated with microsomes and a NADPH-generating system for 0-15 min, and then the extent of inhibition towards seven CYP isoforms were examined.
  
  
  RESULTS
  Star fruit juice (5.0%, v/v) was found to inhibit all the activities of CYP isoforms tested by more than 70%. Based on the half inhibition values (%, v/v), the inhibitory effects towards different CYP isoforms were in the following order: CYP2A6 (0.9) > CYP1A2 (1.4) > CYP2D6 (1.6) > CYP2E1 (2.0) > CYP2C8 (2.2) > CYP2C9 (3.0) > CYP3A4 (3.2). Time-dependent inhibition was not observed towards any of the tested CYP isoforms. In addition, star fruit juice was found not to inhibit the activity of CPR.
  
  
  CONCLUSIONS
  Star fruit juice inhibited the seven CYP isoforms tested, with the strongest inhibitory effect against CYP2A6 and the least towards CYP3A4.
authors.affiliation: 1Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy ofSciences, Zhongshan Road, Dalian, China.
authors.forename: Jiang-Wei
authors.initials: JW
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wang
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: He
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zheng-Tao
authors.initials: ZT
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
mesh_terms: D000328:Adult; D001628:Beverages; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D019684:Magnoliopsida / Q000737:chemistry / Q000502:physiology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System