scholarly journals Inhibition of Human Cytochrome P450 Enzymes by Allergen RemovedRhus vernicifluaStoke Standardized Extract and Constituents

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Hyunsik Jung ◽  
Sanghun Lee
Keyword(s):  
Cytochrome P450 ◽  
Drug Efficacy ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Effects ◽  
Serious Adverse Events ◽  
Rhus Verniciflua ◽  
Human Cytochrome ◽  
Cyp Isoforms ◽  
Inhibitory Potential ◽  
Potential Interactions

Objective. Potential interactions between herbal extracts and the cytochrome P450 (CYP) system lead to serious adverse events or decreased drug efficacy.Rhus vernicifluastoke (RVS) and its constituents have been reported to have various pharmacological properties. We evaluated the inhibitory potential of RVS and its constituents on the major CYP isoforms.Methods. The effects of allergen removed RVS (aRVS) standardized extract and major components, fustin and fisetin isolated from aRVS, were evaluated on CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 isoenzyme activity by a luminescent CYP recombinant human enzyme assay.Results. The aRVS extract showed relative potent inhibitory effects on the CYP2C9 (IC50, <0.001 μg/mL), CYP2C19 (IC50, 9.68 μg/mL), and CYP1A2 (IC50, 10.0 μg/mL). However, it showed weak inhibition on CYP3A4 and CYP2D6. Fustin showed moderate inhibitory effects on the CYP2C19 (IC50, 64.3 μg/mL) and weak inhibition of the other CYP isoforms similar to aRVS. Fisetin showed potent inhibitory effects on CYP2C9, CYP2C19, and CYP1A2. Fisetin showed moderate inhibition of CYP2D6 and weak inhibition of CYP3A4.Conclusions. These results indicate that aRVS, a clinically available herbal medicine, could contribute to herb-drug interactions when orally coadministered with drugs metabolized by CYP2C9, CYP2C19, and CYP1A2.

Inhibitory effects of gypenosides on seven human cytochrome P450 enzymes in vitro

2013 ◽  
Vol 57 ◽  
pp. 262-265 ◽  
Author(s):  
Min He ◽  
Jian Jiang ◽  
Furong Qiu ◽  
Songcan Liu ◽  
Peng Peng ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Effects ◽  
Human Cytochrome

Inhibitory effects of limonin on six human cytochrome P450 enzymes and P-glycoprotein in vitro

2011 ◽  
Vol 25 (8) ◽  
pp. 1828-1833 ◽  
Author(s):  
Yong-Long Han ◽  
Hong-Liang Yu ◽  
Dan Li ◽  
Xiang-Le Meng ◽  
Zhi-Yong Zhou ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Effects ◽  
P Glycoprotein ◽  
Human Cytochrome

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.

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

Pharmacology ◽  
2019 ◽  
Vol 104 (5-6) ◽  
pp. 296-302 ◽  
Author(s):  
Lei Wang ◽  
Xiuju Ma ◽  
Jing Wang ◽  
Chang Li
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Kinetic Studies ◽  
Competitive Inhibitor ◽  
Cytochrome P450 Enzymes ◽  
Inhibitory Effects ◽  
Liver Cytochrome ◽  
Cyp Isoforms

Introduction: Cynaroside is a biological component isolated from Lonicera japonica Thunb, and it possesses numerous pharmacological activities. However, whether cynaroside affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. The purpose of this study was to investigate the effects of cynaroside on 8 major CYP isoforms in human liver microsomes (HLMs). Methods: In this study, the inhibitory effects of cynaroside on the 8 human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using HLMs. Results: The results showed that cynaroside inhibited the activity of CYP1A2, 3A4, and 2C9, with IC50 values of 21.74, 15.88, and 16.58 μmol/L, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that cynaroside was not only a noncompetitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP1A2 and 2C9, with Ki values of 7.33, 11.60, and 8.09 μmol/L, respectively. In addition, cynaroside is a time-dependent inhibitor for CYP3A4 with Kinact/KI value of 0.049/11.62 μmol/L–1min–1. Conclusion: The in vitro studies of cynaroside with CYP isoforms indicate that cynaroside has the potential to cause pharmacokinetic drug interactions with other coadministered drugs metabolized by CYP1A2, 3A4, and 2C9. Further clinical studies are needed to evaluate the significance of this interaction.

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