Pharmaceutical Research

, Volume 33, Issue 3, pp 590–602

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

  • Shufan Ge
  • Taijun Yin
  • Beibei Xu
  • Song Gao
  • Ming Hu
Research Paper

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.

KEY WORDS

BCRP curcumin MRP2 phase II disposition resveratrol 

ABBREVIATIONS

ABC

ATP-binding cassette

AUC

Area under the plasma concentration curve

BCRP/Bcrp

Breast cancer resistance protein

HBSS

Hanks’ balanced salt solution

MRP

Multidrug resistance-associated protein

MS/MS

Tandem mass spectrometry

N.A.

Not available.

PAPS

β-glucuronidases, sulfatase, 3′-Phosphoadenosine 5′-phosphosulfate

RES-3-O-G

Resveratrol-3-O-glucuronide

RES-3-O-S

Resveratrol-3-O-sulfate

RES-4′-O-G

Resveratrol-4′-O-glucuronide

RES-4′-O-S

Resveratrol-4′-O-sulfate

SULT

Sulfotransferase

UDPGA

Uridine diphosphoglucuronic acid

UGT

UDP-glucuronosyltransferase

UPLC

Ultraperformance liquid chromatography

WT

Wild type

Supplementary material

11095_2015_1812_MOESM1_ESM.docx (378 kb)
Supplemental Fig. S1(DOCX 378 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Shufan Ge
    • 1
  • Taijun Yin
    • 1
  • Beibei Xu
    • 1
  • Song Gao
    • 1
  • Ming Hu
    • 1
  1. 1.Department of Pharmacological and Pharmaceutical Sciences, College of PharmacyThe University of HoustonHoustonUSA

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