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

Abstract

Aim: To clarify the cause of poor oral absorption of ginsenoside Rg 1 (Rg 1 ), 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 Rg 1 in rats were compared to evaluate the first-pass effects in the stomach, intestine, and liver. Results: Uptake 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 Rg 1 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 (C 0 =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 Rg 1 , but low membrane permeability might be a more important factor in determining the extent of absorption.

Red Ginseng Saponin Extract Attenuates Murine Collagen-Induced Arthritis by Reducing Pro-inflammatory Responses and Matrix Metalloproteinase-3 Expression

“…MMP-3 expression in the joints of the CIA mice was also reduced substantially by the administration of RGSE. Despite low oral absorption and bioavailability of Rg3 and other ginsenosides [31][32][33] , RGSE at 10 mg/kg was concluded to possess a potent anti-arthritic activity, decreasing inflammation in synovial tissues and blocking the destruction of cartilage and bone via the expression of MMP-3. Rg3, rather than other ginsenosides, may contribute to anti-arthritic activity of RGSE.…”

Ginsenoside Rh1: A Systematic Review of Its Pharmacological Properties

“…However, this contradicted the results of a previous study by Lai et al [85], which investigated the pharmacokinetic parameters and bioavailability of G-Rh1 using intravenous and intragastrical administrations in Sprague-Dawley rats. They found that this compound exhibited extremely poor absolute bioavailability of about 1 % and rapid clearance with a short elimination half-life as can be seen in other protopanaxatriol ginsenosides [86]. The phenomenon might be partly explained by its main metabolic pathways, including CYP450-catalyzed mono-oxygenation, the intestinal bacteria mediated deglucosylation, and the gastric acid mediated hydration reaction [85].…”

Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration

“…The cumulative release of free Sal B and Rg 1 decreased at 6 hours and 8 hours, respectively, which may be due to their own degradation. 34,35 Nanoparticle formulations exhibited a biphasic pattern of drug release for Sal B, R 1 , Rg 1 , and Rb 1 : burst release and sustained release. An initial burst release may be attributed to the immediate release of the surface-associated drug, and a prolonged release in the later stage is due to the slow diffusion of drug from the matrix.…”