In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes
Context Lysionotin, a major extraction of Lysionotus pauciflorus Maxim (Gesneriaceae), has a variety of pharmacological properties commonly used in the treatment of lung disease. A study of lysionotin on the activity of human liver cytochrome P450 (CYP) enzymes can provide guidance on the clinical a...
| 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/10.1080/13880209.2020.1787468 |
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| author | Yang Li Jing Qin Hong Wu Yongmei Xu Li Zhang Keren Su Ying Cui Haiping Wang |
| author_facet | Yang Li Jing Qin Hong Wu Yongmei Xu Li Zhang Keren Su Ying Cui Haiping Wang |
| author_sort | Yang Li |
| collection | DOAJ |
| description | Context Lysionotin, a major extraction of Lysionotus pauciflorus Maxim (Gesneriaceae), has a variety of pharmacological properties commonly used in the treatment of lung disease. A study of lysionotin on the activity of human liver cytochrome P450 (CYP) enzymes can provide guidance on the clinical application of lysionotin. Objective This study investigated the interaction between lysionotin and CYPs. Material and method The effects of 100 μM lysionotin 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 inhibitor as positive control and untreated HLMs as control. Meanwhile, the enzyme kinetic parameters were calculated. A time-dependent study was performed with a time interval of 5 min in 30 min. Results Lysionotin was found to inhibit the activity of CYP3A4, 2C19, and 2C8, with IC50 values of 13.85, 24.95, and 30.05 μM, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with the Ki value of 6.83 μM, while the inhibition of CYP2C19 and 2C8 was performed in a competitive manner with Ki values of 12.41 and 14.51 μM. Moreover, it was found that the inhibition of CYP3A4 was time-dependent with KI/Kinact value of 6.618/0.048 min/μM. Discussion and conclusions: The in vitro inhibitory effect of lysionotin on the activity of CYP3A4, 2C19, and 2C8 indicated potential drug interactions between lysionotin and drugs metabolised by CYP3A4, 2C19, and 2C8. Further in vivo experiments are needed to assess the potential interactions. |
| first_indexed | 2024-12-19T02:11:08Z |
| format | Article |
| id | doaj.art-8522f3af257146e19c0edeff6588ba59 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-19T02:11:08Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-8522f3af257146e19c0edeff6588ba592022-12-21T20:40:44ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162020-01-0158169570010.1080/13880209.2020.17874681787468In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymesYang Li0Jing Qin1Hong Wu2Yongmei Xu3Li Zhang4Keren Su5Ying Cui6Haiping Wang7Department of Neurology, The Affiliated Hospital of Qingdao UniversityDepartment of Laboratory, Yidu Central Hospital of WeifangDepartment of Oncology, Binzhou Medical University HospitalDepartment of Cardiology, Shanxian Central HospitalDepartment of Pharmacy, Shanxian Central HospitalDepartment of Pharmacy, Shanxian Central HospitalDepartment of Hematology and Nephrology, Shanxian Central HospitalDepartment of Neurology, The Affiliated Hospital of Qingdao UniversityContext Lysionotin, a major extraction of Lysionotus pauciflorus Maxim (Gesneriaceae), has a variety of pharmacological properties commonly used in the treatment of lung disease. A study of lysionotin on the activity of human liver cytochrome P450 (CYP) enzymes can provide guidance on the clinical application of lysionotin. Objective This study investigated the interaction between lysionotin and CYPs. Material and method The effects of 100 μM lysionotin 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 inhibitor as positive control and untreated HLMs as control. Meanwhile, the enzyme kinetic parameters were calculated. A time-dependent study was performed with a time interval of 5 min in 30 min. Results Lysionotin was found to inhibit the activity of CYP3A4, 2C19, and 2C8, with IC50 values of 13.85, 24.95, and 30.05 μM, respectively. The inhibition of CYP3A4 was performed in a non-competitive manner with the Ki value of 6.83 μM, while the inhibition of CYP2C19 and 2C8 was performed in a competitive manner with Ki values of 12.41 and 14.51 μM. Moreover, it was found that the inhibition of CYP3A4 was time-dependent with KI/Kinact value of 6.618/0.048 min/μM. Discussion and conclusions: The in vitro inhibitory effect of lysionotin on the activity of CYP3A4, 2C19, and 2C8 indicated potential drug interactions between lysionotin and drugs metabolised by CYP3A4, 2C19, and 2C8. Further in vivo experiments are needed to assess the potential interactions.http://dx.doi.org/10.1080/13880209.2020.1787468cyp3a4cyp2c19cyp2c8drug-drug interaction |
| spellingShingle | Yang Li Jing Qin Hong Wu Yongmei Xu Li Zhang Keren Su Ying Cui Haiping Wang In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes Pharmaceutical Biology cyp3a4 cyp2c19 cyp2c8 drug-drug interaction |
| title | In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes |
| title_full | In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes |
| title_fullStr | In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes |
| title_full_unstemmed | In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes |
| title_short | In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes |
| title_sort | in vitro inhibitory effect of lysionotin on the activity of cytochrome p450 enzymes |
| topic | cyp3a4 cyp2c19 cyp2c8 drug-drug interaction |
| url | http://dx.doi.org/10.1080/13880209.2020.1787468 |
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