In vitro inhibitory effect of lysionotin on the activity of cytochrome P450 enzymes.
Pharm Biol
; 58(1): 695-700, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-32673137
ABSTRACT
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 ANDMETHOD:
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 K I/K inact value of 6.618/0.048 min/µM. Discussion andconclusions:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
/
Microssomos Hepáticos
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Sistema Enzimático do Citocromo P-450
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Flavonas
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Inibidores das Enzimas do Citocromo P-450
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China