Assessment of the inhibition risk of shikonin on cytochrome P450 via cocktail inhibition assay.
Toxicol Lett
; 281: 74-83, 2017 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-28941798
ABSTRACT
Shikonin is a naphthoquinone pigment extracted from roots of Lithospermum erythrorhizon Sieb. et Zucc. (Boraginaceae), and possesses various pharmaceutical activities, such as anti-inflammation and anti-cancer effects. In addition, shikonin as a natural red colorant for food garnishment and cosmetics ingredient is widely used in the world. However, the inhibition risk of shikonin on cytochrome P450 (CYP) remains unclear. The aim of this study was to investigate the potential inhibition of shikonin against CYP1A2, CYP2B1/6, CYP2C9/11, CYP2D1/6, CYP2E1 and CYP3A2/4 activities in human and rat liver microsomes through cocktail approach in vitro. The results demonstrated that shikonin exhibited no time-dependent inhibition of CYP activities. In human liver microsomes, shikonin was not only a mixed inhibitor of CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4, but also a competitive inhibitor of CYP2E1, with Ki values no more than 7.72µM. In rat liver microsomes, shikonin also exhibited the mixed inhibition on CYP1A2, CYP2B1, CYP2C11, CYP2D1, and the competitive inhibition on CYP2E1. Interestingly, shikonin presented an atypical kinetic inhibition of CYP3A2-mediated midazolam 1-hydroxylation in rats. In conclusion, the relatively low Ki values of shikonin would have a high risk potential to cause the possible toxicity, especially drug-drug or food-drug interactions based on the potent inhibition of CYP enzymes.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microssomos Hepáticos
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Naftoquinonas
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Sistema Enzimático do Citocromo P-450
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Inibidores das Enzimas do Citocromo P-450
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Toxicol Lett
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China