Received for publication June 27, 2006.
Revised September 19, 2006.
Accepted for publication September 20, 2006.

Peracetylation as a Means of Enhancing In vitro Bioactivity and Bioavailability of Epigallocatechin-3-gallate

Abstract

(-)-Epigallocatechin-3-gallate (EGCG) is the widely studied catechin in green tea (Camellia sinensis). Previously, we have reported the low bioavailability of EGCG in rats and mice. As a means of improving the bioavailability of EGCG, we have prepared a peracetylated EGCG derivative (AcEGCG), and herein, report its growth inhibitory activity and cellular uptake in vitro, as well as, bioavailability in mice. AcEGCG exhibited enhanced growth inhibitory activity relative to EGCG in both KYSE150 human esophageal (IC₅₀ = 10 vs. 20 µM) and HCT116 human colon cancer cells (IC₅₀ = 32 vs. 45 µM). AcEGCG was rapidly converted to EGCG by HCT116 cells, and treatment of cells with AcEGCG resulted in a 2.8 - 30-fold greater intracellular concentration of EGCG as compared to treatment with EGCG. AcEGCG was also more potent than EGCG at inhibiting nitric oxide-production (4.4-fold) and arachidonic acid-release (2.0-fold) from lipopolysaccharide-stimulated RAW264.7 murine macrophages. Intragastric administration of AcEGCG to CF-1 mice resulted in higher bioavailability compared to administration of equimolar doses of EGCG. The plasma AUC₀ of total EGCG was 465.0 and 194.6 ((µg/mL).min) from the administration of AcEGCG and EGCG, respectively. The t_1/2 of EGCG was also increased following administration of AcEGCG compared to EGCG (441.0 vs. 200.3 min). The AUC₀ and t_1/2 were also increased in small intestinal (2.8- and 4.3-fold, respectively) and colonic tissues (2.4 and 6.0-fold, respectively). These data suggest that acetylation represents a means of increasing the biological potency in vitro, increasing the bioavailability of EGCG in vivo, and may improve cancer preventive activity.

Key words: acetylation, bioactivation, bioavailability, HPLC, pharmacokinetics

This article has been cited by other articles:

				S. M. Henning, J. J. Choo, and D. Heber Nongallated Compared with Gallated Flavan-3-ols in Green and Black Tea Are More Bioavailable J. Nutr., August 1, 2008; 138(8): 1529S - 1534S. [Abstract] [Full Text] [PDF]

				K. R. Landis-Piwowar, C. Huo, D. Chen, V. Milacic, G. Shi, T. H. Chan, and Q. P. Dou A Novel Prodrug of the Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent Cancer Res., May 1, 2007; 67(9): 4303 - 4310. [Abstract] [Full Text] [PDF]