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CYPs-mediated drug-drug interactions on psoralidin, isobavachalcone, neobavaisoflavone and daidzein in rats liver microsomes.
- Source :
-
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2020 Feb; Vol. 136, pp. 111027. Date of Electronic Publication: 2019 Dec 21. - Publication Year :
- 2020
-
Abstract
- The incubation system of CYP2E1 and CYP3A4 enzymes in rat liver microsomes was established to investigate the effects of psoralidin, isobavachalcone, neobavaisoflavone and daidzein from Fructus Psoraleae in vitro. The relevant metabolites were measured by the method of high performance liquid chromatography (HPLC), after probe substrates of 4-nitrophenol, testosterone and the drugs at different concentrations were added to the incubation systems. In addition, real-time RT-PCR was performed to determine the effect of psoralidin, neobavaisoflavone and daidzein on the mRNA expression of CYP3A4 in rat liver. The results suggested that psoralidin, isobavachalcone and neobavaisoflavone were Medium-intensity inhibitors of CYP2E1 with K <subscript>i</subscript> values of 2.58, 1.28 and 19.07 μM, respectively, which could inhibit the increase of CYP2E1 and reduce diseases caused by lipid peroxidation. Isobavachalcone (K <subscript>i</subscript>  = 37.52 μM) showed a weak competitive inhibition on CYP3A4. Psoralidin and neobavaisoflavone showed obvious induction effects on CYP3A4 in the expression level of mRNA, which could accelerate the effects of drug metabolism and lead to the risk of inducing DDIs and serious adverse reactions. The results could be used for guideline of Fructus Psoraleae in clinic, which aimed to calculate the drug toxicity by studying the drug-drug interactions caused by the induction and inhibition of CYP450.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Benzofurans metabolism
Chalcones metabolism
Coumarins metabolism
Cytochrome P-450 CYP2E1 Inhibitors metabolism
Cytochrome P-450 CYP2E1 Inhibitors toxicity
Cytochrome P-450 CYP3A Inhibitors metabolism
Cytochrome P-450 CYP3A Inhibitors toxicity
Drug Interactions
Isoflavones metabolism
Rats, Sprague-Dawley
Benzofurans toxicity
Chalcones toxicity
Coumarins toxicity
Cytochrome P-450 CYP2E1 metabolism
Cytochrome P-450 CYP3A metabolism
Isoflavones toxicity
Microsomes, Liver metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-6351
- Volume :
- 136
- Database :
- MEDLINE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Publication Type :
- Academic Journal
- Accession number :
- 31870919
- Full Text :
- https://doi.org/10.1016/j.fct.2019.111027