scholarly journals Inhibition of Human Liver Cytochrome P450 by Star Fruit Juice

2007 ◽  
Vol 10 (4) ◽  
pp. 496 ◽  
Author(s):  
Jiang-Wei Zhang ◽  
Yong Liu ◽  
Jie Cheng ◽  
Wei Li ◽  
Hong Ma ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Fruit Juice ◽  
Liver Microsomes ◽  
Time Dependent ◽  
Inhibitory Effects ◽  
Star Fruit ◽  
Dependent Inhibition ◽  
Cyp Isoforms ◽  
Time Dependent Inhibition

Purpose. To examine the inhibitory effects of star fruit (Averrhoa carambola) juice towards seven major cytochrome P450 (CYP) isoforms and NADPH-cytochrome P450 reductase (CPR). Methods. The inhibitory effects of star fruit juice (0.5 to 5%, v/v) against the activities of seven CYP isoforms including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP3A4 and CPR were examined in human liver microsomes. To identify time-dependent inhibition, star fruit juice (2.5%, v/v) was preincubated with microsomes and a NADPH-generating system for 0-15 min, and then the extent of inhibition towards seven CYP isoforms were examined. Results. Star fruit juice (5.0%, v/v) was found to inhibit all the activities of CYP isoforms tested by more than 70%. Based on the half inhibition values (%, v/v), the inhibitory effects towards different CYP isoforms were in the following order: CYP2A6 (0.9) > CYP1A2 (1.4) > CYP2D6 (1.6) > CYP2E1 (2.0) > CYP2C8 (2.2) > CYP2C9 (3.0) > CYP3A4 (3.2). Time-dependent inhibition was not observed towards any of the tested CYP isoforms. In addition, star fruit juice was found not to inhibit the activity of CPR. Conclusions. Star fruit juice inhibited the seven CYP isoforms tested, with the strongest inhibitory effect against CYP2A6 and the least towards CYP3A4.

Effect of Solvents on the Time-Dependent Inhibition of CYP3A4 and the Biotransformation of AZD3839 in Human Liver Microsomes and Hepatocytes

2012 ◽  
Vol 41 (1) ◽  
pp. 159-169 ◽  
Author(s):  
Jenny Aasa ◽  
Yin Hu ◽  
Göran Eklund ◽  
Anders Lindgren ◽  
Pawel Baranczewski ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Time Dependent ◽  
Effect Of Solvents ◽  
Dependent Inhibition ◽  
Time Dependent Inhibition

scholarly journals Comprehensive Investigation of Stereoselective Food Drug Interaction Potential of Resveratrol on Nine P450 and Six UGT Isoforms in Human Liver Microsomes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1419
Author(s):  
Seung-Bae Ji ◽  
So-Young Park ◽  
Subin Bae ◽  
Hyung-Ju Seo ◽  
Sin-Eun Kim ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Human Liver ◽  
Liver Microsomes ◽  
Cytochrome P450s ◽  
Human Liver Microsomes ◽  
Time Dependent ◽  
Dependent Manner ◽  
Dependent Inhibition ◽  
Drug Inhibition ◽  
Time Dependent Inhibition

The stereoselectivity of the food drug inhibition potential of resveratrol on cytochrome P450s and uridine 5′-diphosphoglucuronosyl transferases was investigated in human liver microsomes. Resveratrol enantiomers showed stereoselective inhibition of CYP2C9, CYP3A, and UGT1A1. The inhibitions of CYP1A2, CYP2B6, and CYP2C19 by resveratrol were stereo-nonselective. The estimated Ki values determined for CYP1A2 were 13.8 and 9.2 μM for trans- and cis-resveratrol, respectively. Trans-resveratrol noncompetitively inhibited CYP3A and UGT1A1 activities with Ki values of 23.8 and 27.4 μM, respectively. Trans-resveratrol inhibited CYP1A2, CYP2C19, CYP2E1, and CYP3A in a time-dependent manner with Ki shift values >2.0, while cis-resveratrol time-dependently inhibited CYP2C19 and CYP2E1. The time-dependent inhibition of trans-resveratrol against CYP3A4, CYP2E1, CYP2C19, and CYP1A2 was elucidated using glutathione as a trapping reagent. This information helped the prediction of food drug interaction potentials between resveratrol and co-administered drugs which are mainly metabolized by UGT1A1, CYP1A2, CYP2C19, CYP2E1, and CYP3A.

In vitro Inhibitory Effects of Isofraxidin on Human Liver Cytochrome P450 Enzymes

Pharmacology ◽  
2018 ◽  
Vol 103 (3-4) ◽  
pp. 120-127 ◽  
Author(s):  
Xiaoli Song ◽  
Gang Dong ◽  
Yun Zhou
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Kinetic Studies ◽  
Competitive Inhibitor ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Effects ◽  
Liver Cytochrome ◽  
Cyp Isoforms

Isofraxidin is a Coumarin compound widely distributed in plants, such as the Umbelliferae or Chloranthaceae, and it possesses numerous pharmacological activities. However, whether isofraxidin affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. In this study, the inhibitory effects of isofraxidin on the 8 human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes. The results showed that isofraxidin inhibited the activity of CYP1A2, 3A4, and 2E1, with IC50 values of 23.01, 15.49, and 15.98 µmol/L, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that isofraxidin was not only a noncompetitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP1A2 and 2E1, with Ki values of 7.91, 10.14, and 9.30 µmol/L, respectively. In addition, isofraxidin is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.047/12.33 µmol/L–1min–1. The in vitro studies of isofraxidin with CYP isoforms indicate that isofraxidin has the potential to cause pharmacokinetic drug interactions with other coadministered drugs metabolized by ­CYP1A2, 3A4, and 2E1. Further clinical studies are needed to evaluate the significance of this interaction.

scholarly journals Inhibitory Effects of Schisandra Lignans on Cytochrome P450s and Uridine 5′-Diphospho-Glucuronosyl Transferases in Human Liver Microsomes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 371
Author(s):  
Hyung-Ju Seo ◽  
Seung-Bae Ji ◽  
Sin-Eun Kim ◽  
Gyung-Min Lee ◽  
So-Young Park ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Hepatoprotective Activity ◽  
Human Liver Microsomes ◽  
Time Dependent ◽  
Dependent Manner ◽  
Dependent Inhibition ◽  
Night Sweats ◽  
Gomisin A ◽  
Time Dependent Inhibition

Schisandra chinensis has been widely used as a traditional herbal medicine to treat chronic coughs, fatigue, night sweats, and insomnia. Numerous bioactive components including lignans have been identified in this plant. Lignans with a dibenzocyclooctadiene moiety have been known to possess anti-cancer, anti-inflammatory, and hepatoprotective activity. Fragmentary studies have reported the ability of some lignans to modulate some cytochrome P450 (P450) enzymes. Herein, we investigated the drug interaction potential of six dibenzocyclooctadiene lignans (schisandrin, gomisin A, B, C, and N, and wuweizisu C) on nine P450 enzymes (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A) and six uridine 5′-diphosphoglucuronosyl transferase (UGT) enzymes (UGT1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) using human liver microsomes. We found that lignans with one or two methylenedioxyphenyl groups inhibited CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2E1 activities in a time- and concentration-dependent like their CYP3A inhibition. In comparison, these lignans do not induce time-dependent inhibition of CYP1A2, CYP2A6, and CYP2D6. The time-dependent inhibition of gomisin A against CYP2C8, CYP2C19, and CYP3A4 was also elucidated using glutathione as a trapping reagent of reactive carbene metabolites given that gomisin A strongly inhibits these P450 enzymes in a time-dependent manner. A glutathione conjugate of gomisin A was generated in reactions with human recombinant CYP2C8, CYP2C19, and CYP3A4. This suggests that the time-dependent inhibition of gomisin A against CYP2C8, CYP2C9, and CYP3A4 is due to the production of carbene reactive metabolite. Six of the lignans we tested inhibited the activities of six UGT to a limited extent (IC50 > 15 μM). This information may aid the prediction of possible drug interactions between Schisandra lignans and any co-administered drugs which are mainly metabolized by P450s.

Time dependent inhibition of P450 by phenelzine in human liver microsomes

2018 ◽  
Vol 33 (1) ◽  
pp. S34
Author(s):  
Mandy Xu ◽  
Yu Wang ◽  
Cui Yuan ◽  
Danxi Li ◽  
Stephen Harris
Keyword(s):  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Time Dependent ◽  
Dependent Inhibition ◽  
Time Dependent Inhibition
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