Acta Pharmacologica Sinica 2006 April; 27 (4): 499-505; doi: 10.1111/j.1745-7254.2006.00303.x

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 Rg₁ 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: Uptake of Rg₁ 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 Rg₁. 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 (2.59±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.

Keywords: ginsenoside Rg1; Panax; Caco-2; bioavaila-bility; pharmacokinetics