Abstract
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:
Up take 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 (2.5 9±0.17) × 10−7 cm/s (C0=1 mg/mL) predicted incomplete absorption. A significant difference was observed between the po (Fpo was 3.29% at a dose of 1500 mg/kg), id Fid was 6.60% at a dose of 1200 mg/kg) and pv (FPV 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.
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Han, M., Fang, Xl. Difference in oral absorption of ginsenoside Rg1 between in vitro and in vivo models. Acta Pharmacol Sin 27, 499–505 (2006). https://doi.org/10.1111/j.1745-7254.2006.00303.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00303.x
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