Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies

@article{Zhuang2013IdentificationAC,
  title={Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies},
  author={Xiaomei Zhuang and Yuhuan Zhong and Weibin Xiao and Hua Li and Chuang Lu},
  journal={Drug Metabolism and Disposition},
  year={2013},
  volume={41},
  pages={1914 - 1922}
}
Naturally occurring furanocoumarin compounds psoralen (PRN) and isopsoralen (IPRN) are bioactive constituents found in herbaceous plants. They are widely used as active ingredients in several Chinese herbal medicines. In this study, the CYP1A2 inhibitory potential of PRN and IPRN was investigated in rats in vitro and in vivo as well as in human liver microsomes. Both compounds exhibited reversible and time-dependent inhibition toward rat microsomal cyp1a2. The IC50, kinact, and KI values were… Expand
Psoralen, a mechanism-based inactivator of CYP2B6.
TLDR
PRN was characterized as a mechanism-based inactivator of CYP2B6, and GSH trapping experiments indicates that an epoxide or/and γ-ketoenal intermediate was formed in microsomal incubations with PRN. Expand
Selective Inhibition of Bakuchicin Isolated from Psoralea corylifolia on CYP1A in Human Liver Microsomes
TLDR
The inhibitory effects of bakuchicin on the activities of CYP isoforms by using a cocktail of probe substrates in pooled human liver microsomes (HLMs) and human recombinant cDNA-expressed CYP and the inhibition mechanism was competitive inhibition. Expand
Mechanism-based inactivation of cytochrome P450 2B6 by isopsoralen
TLDR
The GSH trapping experiments indicate that an epoxide and/or γ-ketoenal intermediate were/was generated in IPRN-fortified microsomal incubations and may be responsible for the inactivation of CYP2B6. Expand
In vitro inhibitory effect of piperlonguminine isolated from Piper longum on human cytochrome P450 1A2
TLDR
This is the first investigation of potential herb–drug interactions associated with PL conducted by identifying the competitive inhibitory effects of PL on CYP1A2 in HLMs. Expand
Potential Mechanism of Herb-Drug Interaction Mediated by Angelica dahurica: Inhibition on CYP3A Enzymes in Rats
Angelica dahurica is commonly referred to as ‘Baizhi’ in China and has been noted for its therapeutic significance. The major active ingredients of Angelica dahurica is coumarin, which is reported asExpand
Studies on the metabolites difference of psoralen/isopsoralen in human and six mammalian liver microsomes in vitro by UHPLC–MS/MS
TLDR
The results show that the metabolic capability of human for Psoralen and isopsoralen are weaker than other mammal species, and the most relevant animal species for investigation of psoralen/isopsolaren from experimental animals to human is chosen. Expand
High hepatic exposure of furanocoumarins in Radix Angelica dahuricae is associated with transporter mediated active uptake.
TLDR
IM, IIM, BER and OXYH were found to be the major bioactive furanocoumarins in rat plasma and tissues, representing more than 90% exposure for all the detected furano-marins. Expand
Mechanism-based inactivation of cytochrome P450 2B6 by isoimperatorin.
TLDR
Isoimperatorin is a mechanism-based inactivator of CYP2B6 and the formation of γ-ketoenal intermediate may be responsible for the enzyme inactivation. Expand
Identification of karanjin isolated from the Indian beech tree as a potent CYP1 enzyme inhibitor with cellular efficacy via screening of a natural product repository.
TLDR
Isopimpinellin and karanjin showed the most potent inhibition of CYP1A1 in human cells, and molecular docking and molecular dynamic simulations with CYP isoforms rationalize the observed trends in the potency and selectivity. Expand
Imperatorin Is a Mechanism-Based Inactivator of CYP2B6
TLDR
IMP is a mechanism-based inactivator of CYP2B6 and the formation of γ-ketoenal intermediate may account for the enzyme inactivation. Expand
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