Welcome to LookChem.com Sign In | Join Free

Science Details

Home > Chemical Encyclopedia > Science List > Details
  • RESEARCH ARTICLE: Pharmacokinetics, Pharmacodynamics and Drug Transport and MetabolismRegio- and Isoform-Specific Glucuronidation of psoralidin (cas 18642-23-4): Evaluation of 3-O-Glucuronidation as a Functional Marker for UGT1A9

  • Add time:09/25/2019    Source:sciencedirect.com

    ABSTRACTIn th is study, we aimed to determine the glucuronidation potential of psoralidin in humans and to perform validation on use of psoralidin-3-O-glucuronidation as afunctional marker for UGT1A9. Glucuronidation kinetics was determined using human liver microsomes (HLMs), human intestine microsomes (HIM), and expressed UDP-glucuronosyltransferase (UGT) enzymes. The chemical structures of metabolites were determined by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy analyses. Validation of psoralidin-3-O-glucuronidation as a UGT1A9 marker was performed using combined approaches including reaction phenotyping, chemical inhibition, activity correlation analysis, and determination of relative activity factor (RAF). HLM and UGT1A9 generated two monoglucuronides (9-O-glucuronide and 3-O-glucuronide) from psoralidin, whereas HIM, UGT1A1, UGT1A7, and UGT1A8 generated one only (9-O-glucuronide). Formation of 3-O-glucuronide in HLM was markedly inhibited by the UGT1A9-selective inhibitors magnolol and niflumic acid. Further, psoralidin-3-O-glucuronidation was strongly correlated with propofol-glucuronidation in a group of nine individual HLMs (r = 0.978, p < 0.001). Strong correlation was also observed between psoralidin-3-O-glucuronidation and the UGT1A9 protein levels measured by Western blotting (r = 0.944, p < 0.001). Moreover, UGT1A9 was responsible for 99.6% of psoralidin-3-O-glucuronidation in HLM based on the RAF approach. In conclusion, psoralidin was subjected to efficient glucuronidation, generating one or two monoglucuronides depending on UGT isozymes. Also, psoralidin-3-O-glucuronidation was an excellent in vitro marker for UGT1A9.

    We also recommend Trading Suppliers and Manufacturers of psoralidin (cas 18642-23-4). Pls Click Website Link as below: cas 18642-23-4 suppliers

    Prev:Molecular and cellular pharmacologypsoralidin (cas 18642-23-4), a prenylated coumestan, as a novel anti-osteoporosis candidate to enhance bone formation of osteoblasts and decrease bone resorption of osteoclasts
    Next:Comparison of the in vitro metabolism of psoralidin (cas 18642-23-4) among different species and characterization of its inhibitory effect against UDP- glucuronosyltransferase (UGT) or cytochrome p450 (CYP450) enzymes)

  • Back】【Close 】【Print】【Add to favorite
    Related Information
Periodic Table
    Related Products