Difference in oral absorption of ginsenoside Rg₁ between in vitro and in vivo models

Aim: To clarify the cause of poor oral absorption of ginsenoside Rg₁ (Rg₁), the active ingredient in Panax notoginseng saponins (PNS) used for treating hemorrhage. Methods: Caco-2 cell monolayers were used as an in vitro model to study the transport mechanism of Rg ₁ across the intestinal mucosa. Moreover, the serum concentration-time profiles after peroral (po ), intraduodenal (id), portal venous (pv) and tail venous (iv) administration of Rg1 in rats were compared to evaluate the first-pass effects in the stomach, intestine, and liver. Results: Up take of Rg ₁ by Caco-2 cell monolayers was temperature-dependent, but was not influenced by cyclosporin A. The change in the apical pH produced no obvious effect on the uptake of Rg ₁. The uptake and transport of Rg₁ was non-saturable; whereas the flux from the apical compartment to the basolateral compartment (A-B) increased in a linear manner with the increase in concentration, indicating passive transport. An apparent permeability coefficient of (2.5 9 0.17)×10^-7 cm/s (C₀=1 mg/mL) predicted incomplete absorption. A significant difference was observed between the po (F_po was 3.29% at a dose of 1500 mg/kg), id F_id was 6.60% at a dose of 1200 mg/kg) and pv (F_PV was 50.56%) administration methods, and the barrier function of the intestine was more significant than those of the stomach and liver in the absorption process. Conclusion: Elimination in the stomach, large intestine and liver contributed to the low oral bioavailability of Rg₁, but low membrane permeability might be a more important factor in determining the extent of absorption.