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Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes
Joint Authors
Shan, Lina
Zhang, Gang
Shi, Xianbao
Ma, Zhongnv
Guo, Feng
Cai, Jiqun
Source
Evidence-Based Complementary and Alternative Medicine
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-03-10
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Cytochrome p450 (CYP450) enzymes are predominantly involved in Phase I metabolism of xenobiotics.
In this study, the CYP450 isoforms involved in xanthotoxol metabolism were identified using recombinant CYP450s.
In addition, the inhibitory effects of xanthotoxol on eight CYP450 isoforms and its pharmacokinetic parameters were determined using human liver microsomes.
CYP1A2, one of CYP450s, played a key role in the metabolism of xanthotoxol compared to other CYP450s.
Xanthotoxol showed stronger inhibition on CYP3A4 and CYP1A2 compared to other isoenzymes with the IC50 of 7.43 μM for CYP3A4 and 27.82 μM for CYP1A2.
The values of inhibition kinetic parameters (Ki) were 21.15 μM and 2.22 μM for CYP1A2 and CYP3A4, respectively.
The metabolism of xanthotoxol obeyed the typical monophasic Michaelis-Menten kinetics and V m a x , K m , and C L i n t values were calculated as 0.55 nmol·min−1·mg−1, 8.46 μM, and 0.06 mL·min−1·mg−1.
In addition, the results of molecular docking showed that xanthotoxol was bound to CYP1A2 with hydrophobic and π - π bond and CYP3A4 with hydrogen and hydrophobic bond.
We predicted the hepatic clearance ( C L H ) and the C L H value was 15.91 mL·min−1·kg−1 body weight.
These data were significant for the application of xanthotoxol and xanthotoxol-containing herbs.
American Psychological Association (APA)
Ma, Zhongnv& Shi, Xianbao& Zhang, Gang& Guo, Feng& Shan, Lina& Cai, Jiqun. 2016. Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes. Evidence-Based Complementary and Alternative Medicine،Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1104212
Modern Language Association (MLA)
Ma, Zhongnv…[et al.]. Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes. Evidence-Based Complementary and Alternative Medicine No. 2016 (2016), pp.1-8.
https://search.emarefa.net/detail/BIM-1104212
American Medical Association (AMA)
Ma, Zhongnv& Shi, Xianbao& Zhang, Gang& Guo, Feng& Shan, Lina& Cai, Jiqun. Metabolism and Metabolic Inhibition of Xanthotoxol in Human Liver Microsomes. Evidence-Based Complementary and Alternative Medicine. 2016. Vol. 2016, no. 2016, pp.1-8.
https://search.emarefa.net/detail/BIM-1104212
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1104212