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Nutrient Interactions and Toxicity

Piperine Enhances the Bioavailability of the Tea Polyphenol (–)-Epigallocatechin-3-gallate in Mice¹

Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, Piscataway, NJ 08854

²To whom correspondence should be addressed. E-mail: joshua_lambert{at}hotmail.com.

(–)-Epigallocatechin-3-gallate (EGCG), from green tea (Camellia sinensis), has demonstrated chemopreventive activity in animal models of carcinogenesis. Previously, we reported the bioavailability of EGCG in rats (1.6%) and mice (26.5%). Here, we report that cotreatment with a second dietary component, piperine (from black pepper), enhanced the bioavailability of EGCG in mice. Intragastric coadministration of 163.8 µmol/kg EGCG and 70.2 µmol/kg piperine to male CF-1 mice increased the plasma C_max and area under the curve (AUC) by 1.3-fold compared to mice treated with EGCG only. Piperine appeared to increase EGCG bioavailability by inhibiting glucuronidation and gastrointestinal transit. Piperine (100 µmol/L) inhibited EGCG glucuronidation in mouse small intestine (by 40%) but not in hepatic microsomes. Piperine (20 µmol/L) also inhibited production of EGCG-3''-glucuronide in human HT-29 colon adenocarcinoma cells. Small intestinal EGCG levels in CF-1 mice following treatment with EGCG alone had a C_max = 37.50 ± 22.50 nmol/g at 60 min that then decreased to 5.14 ± 1.65 nmol/g at 90 min; however, cotreatment with piperine resulted in a C_max = 31.60 ± 15.08 nmol/g at 90 min, and levels were maintained above 20 nmol/g until 180 min. This resulted in a significant increase in the small intestine EGCG AUC (4621.80 ± 1958.72 vs. 1686.50 ± 757.07 (nmol/g·min)). EGCG appearance in the colon and the feces of piperine-cotreated mice was slower than in mice treated with EGCG alone. The present study demonstrates the modulation of the EGCG bioavailablity by a second dietary component and illustrates a mechanism for interactions between dietary chemicals.

KEY WORDS: • epigallocatechin-3-gallate • piperine • green tea • bioavailability • mice