In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes
Context Cepharanthine (CEP) extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), has a range of therapeutic potential in clinical conditions. Whether it affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods The effects of CEP (...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/13880209.2020.1741650 |
| _version_ | 1818609639740145664 |
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| author | Xunge Zhang Ping Feng Xinfu Gao Bin Wang Chunxia Gou Ruimin Bian |
| author_facet | Xunge Zhang Ping Feng Xinfu Gao Bin Wang Chunxia Gou Ruimin Bian |
| author_sort | Xunge Zhang |
| collection | DOAJ |
| description | Context Cepharanthine (CEP) extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), has a range of therapeutic potential in clinical conditions. Whether it affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods The effects of CEP (100 μM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific probe actions and probe substrates. In addition, the enzyme kinetic parameters were calculated. Results The results showed that the activity of CYP3A4, CYP2E1 and CYP2C9 was inhibited by CEP, with IC50 values of 16.29, 25.62 and 24.57 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that CEP was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2C9, with Ki values of 8.12, 11.78 and 13.06 μM, respectively. Additionally, CEP is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 10.84/0.058 min/μM. Discussion and conclusions The in vitro studies of CEP with CYP isoforms indicate that CEP has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2C9. Further clinical studies are needed to evaluate the significance of this interaction. |
| first_indexed | 2024-12-16T15:01:44Z |
| format | Article |
| id | doaj.art-ed39d1aee88c49778a7164a36aa22255 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-16T15:01:44Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-ed39d1aee88c49778a7164a36aa222552022-12-21T22:27:16ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162020-01-0158124725210.1080/13880209.2020.17416501741650In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymesXunge Zhang0Ping Feng1Xinfu Gao2Bin Wang3Chunxia Gou4Ruimin Bian5Department of Pharmacy, Binzhou Medical University HospitalDepartment of Pharmacy, Binzhou Medical University HospitalDepartment of Pharmacy, Binzhou Medical University HospitalDepartment of Pharmacy, Binzhou Medical University HospitalDepartment of Pharmacy, Binzhou Medical University HospitalDepartment of Pharmacy, Binzhou Medical University HospitalContext Cepharanthine (CEP) extracted from the roots of Stephania cepharantha Hayata (Menispermaceae), has a range of therapeutic potential in clinical conditions. Whether it affects the activity of human liver cytochrome P450 (CYP) enzymes remains unclear. Materials and methods The effects of CEP (100 μM) on eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19 and 2C8) were investigated in vitro using human liver microsomes (HLMs) with specific probe actions and probe substrates. In addition, the enzyme kinetic parameters were calculated. Results The results showed that the activity of CYP3A4, CYP2E1 and CYP2C9 was inhibited by CEP, with IC50 values of 16.29, 25.62 and 24.57 μM, respectively, but other CYP isoforms were not affected. Enzyme kinetic studies showed that CEP was not only a non-competitive inhibitor of CYP3A4 but also a competitive inhibitor of CYP2E1 and CYP2C9, with Ki values of 8.12, 11.78 and 13.06 μM, respectively. Additionally, CEP is a time-dependent inhibitor for CYP3A4 with KI/Kinact value of 10.84/0.058 min/μM. Discussion and conclusions The in vitro studies of CEP with CYP isoforms indicate that CEP has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP3A4, CYP2E1 and CYP2C9. Further clinical studies are needed to evaluate the significance of this interaction.http://dx.doi.org/10.1080/13880209.2020.1741650cyp3a4cyp2e1cyp2c9drug–drug interaction |
| spellingShingle | Xunge Zhang Ping Feng Xinfu Gao Bin Wang Chunxia Gou Ruimin Bian In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes Pharmaceutical Biology cyp3a4 cyp2e1 cyp2c9 drug–drug interaction |
| title | In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes |
| title_full | In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes |
| title_fullStr | In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes |
| title_full_unstemmed | In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes |
| title_short | In vitro inhibitory effects of cepharanthine on human liver cytochrome P450 enzymes |
| title_sort | in vitro inhibitory effects of cepharanthine on human liver cytochrome p450 enzymes |
| topic | cyp3a4 cyp2e1 cyp2c9 drug–drug interaction |
| url | http://dx.doi.org/10.1080/13880209.2020.1741650 |
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