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

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. 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. 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. After intestinal perfusion for 3 h, 9.1% of 20(R)-Rh2 and 15.7% of 20(S)-Rh2 were absorbed. 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. The ABC-transporter-mediated efflux and the poor permeability were the major reasons for Rh2 poor absorption. The stereoselective absorption was significant. R isomer exhibited lower absorption profiles in all the experiments, possibly due to more potent efflux.