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| Content Provider | PubMed Central |
|---|---|
| Author | Lv, Qiao-li Wang, Gui-hua Chen, Shu-hui Lei, Hu Zhang, Xue Ying, Guo Qin, Chong-zhen Zhou, Hong-hao |
| Editor | Chang, Huang-tsung |
| Copyright Year | 2015 |
| Abstract | Glycyrrhetinic acid (GA) has been used clinically in the treatment of patients with chronic hepatitis. This study evaluated the effect of GA on the activity of five P450(CYP450) cytochrome enzymes: CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, in human liver microsomes (HLMs) and recombinant cDNA-expressed enzyme systems using a HPLC-MS/MS CYP-specific probe substrate assay. With midazolam as the probe substrate, GA greatly decreased CYP3A4 activity with IC50 values of 8.195 μM in HLMs and 7.498 μM in the recombinant cDNA-expressed CYP3A4 enzyme system, respectively. It significantly decreased CYP3A4 activity in a dose- but not time-dependent manner. Results from Lineweaver–Burk plots showed that GA could inhibit CYP3A4 activity competitively, with a Ki value of 1.57 μM in HLMs. Moreover, CYP2C9 and CYP2C19 could also be inhibited significantly by GA with IC50 of 42.89 and 40.26 μM in HLMs, respectively. Other CYP450 isoforms were not markedly affected by GA. The inhibition was also confirmed by an in vivo study of mice. In addition, it was observed that mRNA expressions of the Cyps2c and 3a family decreased significantly in the livers of mice treated with GA. In conclusion, this study indicates that GA may exert herb-drug interactions by competitively inhibiting CYP3A4. |
| Related Links | http://dx.doi.org/10.3390/ijerph13010084 |
| Starting Page | 84 |
| File Format | |
| ISSN | 16604601 |
| e-ISSN | 16604601 |
| Journal | International Journal of Environmental Research and Public Health |
| Issue Number | 1 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2015-12-01 |
| Access Restriction | Open |
| Rights Holder | MDPI |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Pollution Public Health, Environmental and Occupational Health |
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