Abstract Title:

Curcumin Affects Phase II Disposition of Resveratrol Through Inhibiting Efflux Transporters MRP2 and BCRP.

Abstract Source:

Pharm Res. 2015 Oct 26. Epub 2015 Oct 26. PMID: 26502886

Abstract Author(s):

Shufan Ge, Taijun Yin, Beibei Xu, Song Gao, Ming Hu

Article Affiliation:

Shufan Ge

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.

Study Type : Animal Study

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