In Vitro Inhibitory Effects of Scutellarin on Six Human/Rat Cytochrome P450 Enzymes and P-glycoprotein
Abstract
:1. Introduction
2. Results and Discussion
Isoenzyme | Substrate | Metabolites | IC50 for HLM | IC50 for RLM |
---|---|---|---|---|
(μM) | (μM) | |||
CYP1A2 | Phenacetin | Acetaminophen | >100 | >100 |
CYP2C8 | Paclitaxel | 6α-Hydroxypaclitaxel | >100 | 63.1[95% CI: 39.3–101.3] |
CYP2C9 | Diclofenac | 4-Hydroxydiclofenac | >100 | >100 |
CYP2C19 | S-Mephenytoin | 4-Hydroxymephenytoin | 63.8 [95% CI: 38.5–105.7] | 85.6[95% CI: 43.5–168.4] |
CYP2D6 | Dextromethorphan | Dextrorphan | >100 | >100 |
CYP3A4 | Midazolam | 1-Hydroxymidazolam | >100 | >100 |
2.1. Inhibition by Scutellarin on Six CYPs in HLM
2.2. Inhibition by Scutellarin on Six CYPs in RLM
2.3. Inhibition by Scutellarin on P-glycoprotein
3. Experimental
3.1. Materials
Unit | Gender | Age (From 21 to 77 Years) | Race | |||||
---|---|---|---|---|---|---|---|---|
Male | Female | ≤39 | 40~49 | 50~59 | ≥60 | Caucasian | African Ameracian | |
Number | 27 | 23 | 8 | 15 | 13 | 14 | 47 | 3 |
3.2. Instrument
3.3. CYP450 Assay
3.3.1. Microsomal Incubations and Treatment Protocol
3.3.2. LC-MS/MS Analysis
3.4. P-glycoprotein Assay [49]
3.5. Data Analysis
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Share and Cite
Han, Y.-L.; Li, D.; Yang, Q.-J.; Zhou, Z.-Y.; Liu, L.-Y.; Li, B.; Lu, J.; Guo, C. In Vitro Inhibitory Effects of Scutellarin on Six Human/Rat Cytochrome P450 Enzymes and P-glycoprotein. Molecules 2014, 19, 5748-5760. https://doi.org/10.3390/molecules19055748
Han Y-L, Li D, Yang Q-J, Zhou Z-Y, Liu L-Y, Li B, Lu J, Guo C. In Vitro Inhibitory Effects of Scutellarin on Six Human/Rat Cytochrome P450 Enzymes and P-glycoprotein. Molecules. 2014; 19(5):5748-5760. https://doi.org/10.3390/molecules19055748
Chicago/Turabian StyleHan, Yong-Long, Dan Li, Quan-Jun Yang, Zhi-Yong Zhou, Li-Ya Liu, Bin Li, Jin Lu, and Cheng Guo. 2014. "In Vitro Inhibitory Effects of Scutellarin on Six Human/Rat Cytochrome P450 Enzymes and P-glycoprotein" Molecules 19, no. 5: 5748-5760. https://doi.org/10.3390/molecules19055748