In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes
Context: Friedelin is a triterpenoid with several biological activities. However, the affects of Friedelin on the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the inhibitory effects of Friedelin on the major human liver CYP isoforms (CYP3A...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2018.1491999 |
| _version_ | 1818683376246194176 |
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| author | Jinlan Wei Hongying Zhang Qingling Zhao |
| author_facet | Jinlan Wei Hongying Zhang Qingling Zhao |
| author_sort | Jinlan Wei |
| collection | DOAJ |
| description | Context: Friedelin is a triterpenoid with several biological activities. However, the affects of Friedelin on the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the inhibitory effects of Friedelin on the major human liver CYP isoforms (CYP3A4, 1A2, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8). Materials and methods: First, the inhibitory effects of Friedelin (100 μM) on the eight human liver CYP isoforms were investigated in vitro using human liver microsomes (HLMs), and then enzyme inhibition, kinetic studies, and time-dependent inhibition studies were conducted to investigate the IC50, Ki and Kinact/KI values of Friedelin. Results: The results indicate that Friedelin inhibited the activity of CYP3A4 and 2E1, with the IC50 values of 10.79 and 22.54 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that Friedelin is not only a noncompetitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1, with Ki values of 6.16 and 18.02 μM, respectively. In addition, Friedelin is a time-dependent inhibitor of CYP3A4 with Kinact/Ki value of 4.84 nM/min. Discussion and conclusion: The in vitro studies of Friedelin with CYP isoforms suggested that Friedelin has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4 and 2E1. Further clinical studies are needed to evaluate the significance of this interaction. |
| first_indexed | 2024-12-17T10:33:45Z |
| format | Article |
| id | doaj.art-7c57a3f19d7743589ef40506ef1a1126 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-17T10:33:45Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-7c57a3f19d7743589ef40506ef1a11262022-12-21T21:52:28ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162018-01-0156136336710.1080/13880209.2018.14919991491999In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymesJinlan Wei0Hongying Zhang1Qingling Zhao2Yidu Central Hospital of WeifangYidu Central Hospital of WeifangYidu Central Hospital of WeifangContext: Friedelin is a triterpenoid with several biological activities. However, the affects of Friedelin on the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Objective: This study investigates the inhibitory effects of Friedelin on the major human liver CYP isoforms (CYP3A4, 1A2, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8). Materials and methods: First, the inhibitory effects of Friedelin (100 μM) on the eight human liver CYP isoforms were investigated in vitro using human liver microsomes (HLMs), and then enzyme inhibition, kinetic studies, and time-dependent inhibition studies were conducted to investigate the IC50, Ki and Kinact/KI values of Friedelin. Results: The results indicate that Friedelin inhibited the activity of CYP3A4 and 2E1, with the IC50 values of 10.79 and 22.54 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that Friedelin is not only a noncompetitive inhibitor of CYP3A4, but also a competitive inhibitor of CYP2E1, with Ki values of 6.16 and 18.02 μM, respectively. In addition, Friedelin is a time-dependent inhibitor of CYP3A4 with Kinact/Ki value of 4.84 nM/min. Discussion and conclusion: The in vitro studies of Friedelin with CYP isoforms suggested that Friedelin has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4 and 2E1. Further clinical studies are needed to evaluate the significance of this interaction.http://dx.doi.org/10.1080/13880209.2018.1491999cyp3a4cyp2e1drug–drug interactions |
| spellingShingle | Jinlan Wei Hongying Zhang Qingling Zhao In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes Pharmaceutical Biology cyp3a4 cyp2e1 drug–drug interactions |
| title | In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes |
| title_full | In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes |
| title_fullStr | In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes |
| title_full_unstemmed | In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes |
| title_short | In vitro inhibitory effects of Friedelin on human liver cytochrome P450 enzymes |
| title_sort | in vitro inhibitory effects of friedelin on human liver cytochrome p450 enzymes |
| topic | cyp3a4 cyp2e1 drug–drug interactions |
| url | http://dx.doi.org/10.1080/13880209.2018.1491999 |
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