Curcumin Affects Phase II Disposition of Resveratrol Through Inhibiting Efflux Transporters MRP2 and BCRP.
Pharm Res
; 33(3): 590-602, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26502886
ABSTRACT
PURPOSE:
To evaluate the impact of curcumin on the disposition of resveratrol phase II metabolites in vivo, and explain the observations by performing in vitro studies in transporter-overexpressed cells.METHODS:
Pharmacokinetic studies of resveratrol with and without the co-administration of curcumin were performed in both FVB wild-type and Bcrp1 (-/-) mice. Human UGT1A9-overexpressing HeLa cells and human MRP2-overexpressing MDCK II-UGT1A1 cells were used as in vitro tools to further determine the impact of curcumin as a transporter inhibitor on resveratrol metabolites.RESULTS:
We observed higher exposure of resveratrol conjugates in Bcrp1 (-/-) mice compared to wild-type mice. In wild-type mice, curcumin increased the AUC of resveratrol glucuronide by 4-fold compared to the mice treated without curcumin. The plasma levels of resveratrol and its sulfate conjugate also increased moderately. In Bcrp1 (-/-) mice, there was a further increase (6-fold increase) in AUC of resveratrol glucuronide observed when curcumin was co-administered compared to AUC values obtained in wild-type mice without curcumin treatment. In the presence of 50 nM curcumin, the clearance of resveratrol-3-O-glucuronide and resveratrol-3-O-sulfate reduced in both MRP2-overexpressing MDCKII-UGT1A1 cells and Human UGT1A9-overexpressing HeLa cells.CONCLUSIONS:
These results suggest that curcumin alters the phase II distribution of resveratrol through inhibiting efflux transporters including MRP2 and BCRP.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estilbenos
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Transportadores de Cassetes de Ligação de ATP
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Curcumina
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Proteínas Associadas à Resistência a Múltiplos Medicamentos
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Desintoxicação Metabólica Fase II
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Proteínas de Neoplasias
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos