Intestinal absorption mechanisms of ginsenoside Rh2: stereoselectivity and involvement of ABC transporters

Abstract

1. This study investigated the absorption mechanism of ginsenoside Rh2 to clarify the reasons for its poor absorption. Transepithelial transport across Caco-2 cell monolayers, cellular uptake, and in situ rat intestinal perfusion were examined.

2. Cellular uptake of Rh2 was linear from 1 to 50 μM at 4°C, whereas it was saturated when the concentration exceeded 10 μM at 37°C. At 37°C, the uptake at 10 μM was linear in 60 min. Intracellular exposure in 240 min was 2173.70 and 979.38 ng·min/μg for S and R isomers, respectively.

3. Transepithelial permeability of Rh2 was about 10⁻⁸ to 10⁻⁷ cm/s. Efflux ratios were above 1.5. Sodium dodecyl sulfate, sodium citrate, and sodium deoxycholate had no effect on Rh2 permeability.

4. After intestinal perfusion for 3 h, 9.1% of 20(R)-Rh2 and 15.7% of 20(S)-Rh2 were absorbed.

5. Cyclosporine, quercetin, and probenecid could improve the cellular uptake, absorptive permeability, and intestinal absorption. Carrier-mediated transport was the major absorption mechanism. Rh2 was a substrate of ABC transporters.

6. The ABC-transporter-mediated efflux and the poor permeability were the major reasons for Rh2 poor absorption.

7. The stereoselective absorption was significant. R isomer exhibited lower absorption profiles in all the experiments, possibly due to more potent efflux.

Keywords::

• Ginsenoside Rh2
• Intestinal Absorption
• Transport
• Caco-2 cells
• ABC transporters
• Stereoselectivity

Acknowledgements

The first author sincerely acknowledged Ms Lei Cai for the support of the manuscript preparation.

Declaration of interest

This research was supported by the National High Technology Foundation of China (863 Project, No. 2003AA2Z347A), the fund of Jiangsu Key Lab of Drug Metabolism and Pharmacokinetics (No. BM2001201) and the Natural Science Foundation of Jiangsu Province (BK 2005098)