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  • Title: Characterization of in vitro metabolites of cudratricusxanthone A in human liver microsomes.
    Author: Sim J, Choi E, Jeong GS, Lee S.
    Journal: Biopharm Drug Dispos; 2015 Jul; 36(5):325-36. PubMed ID: 25765476.
    Abstract:
    Cudratricusxanthone A (CTXA), isolated from the roots of Cudrania tricuspidata, exhibits several biological activities; however, metabolic biotransformation was not investigated. Therefore, metabolites of CTXA were investigated and the major metabolic enzymes engaged in human liver microsomes (HLMs) were characterized using liquid chromatography-tandem mass spectrometry (LC-MS/MS). CTXA was incubated with HLMs or human recombinant CYPs and UGTs, and analysed by an LC-MS/MS equipped electrospray ionization (ESI) to qualify and quantify its metabolites. In total, eight metabolites were identified: M1-M4 were identified as mono-hydroxylated metabolites during Phase I, and M5-M8 were identified as O-glucuronidated metabolites during Phase II in HLMs. Moreover, these metabolite structures and a metabolic pathway were identified by elucidation of MS(n) fragments and formation by human recombinant enzymes. M1 was formed by CYP2D6, and M2-M4 were generated by CYP1A2 and CYP3A4. M5-M8 were mainly formed by UGT1A1, respectively. While investigating the biotransformation of CTXA, eight metabolites of CTXA were identified by CYPs and UGTs; these data will be valuable for understanding the in vivo metabolism of CTXA.
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