Mechanism of oral absorption of panaxnotoginseng saponins

AimTo study the mechanism of absorption after oral administration of panaxnotoginseng saponins (PNS). MethodsCaco-2 cells and rat models were applied to evaluate the degradation of both ginsenoside Rb₁(Rb_l) and ginsenoside Rg₁(Rg_l) in PNS in gastrointestinal lumen, and the transport mechanism of PNS across the intestinal mucosa, and the barrier function of stomach, intestine and liver involved in absorption process. ResultsRb₁and Rg₁proved to be readily eliminated in stomach, but stable in relatively neutral circumstance. Both Rb₁and Rg₁in PNS, especially for Rb_l, degraded significantly in the contents of large intestine. However, both of them kept mainly intact in the contents of small intestine. Uptake of both Rb₁and Rg₁by Caco-2 cell monolayer was inhibited at low temperature, but not by cyclosporine A, and the change in the apical pH showed no pronounced effect. Uptake and transport were non-saturable and increased linearly with increasing of concentrations of Rb₁and Rg₁over the range of concentration tested, which indicated a passive transport. There was no significant difference of absorption characteristic between monomer (Rb₁and Rg_l) and mixture (PNS). Uptake amount of Rg₁［(1.07±0.16) μg·mg^-1(protein)］ (C₀=1 mg·mL^-1) in Caco-2 cells was a little higher than that of Rb₁［(0.77±0.03) μg·mg^-1(protein)］ (C₀=1 mg·mL^-1). Meanwhile, apparent permeability coefficient of (5.9±1.0)×10^{-8cm·s-1(C₀=1 mg·mL-1) for Rb₁and (2.59±0.17)×10-7 cm·s-1 (C₀=1 mg·mL-1) for Rg₁from apical compartment to basolateral compartment predicted an incompletely absorption. Transports of both Rb₁and Rg₁were not influenced by cyclosporine A. The investigation on the pharmacokinetic behavior of Rb₁and Rg₁after different routes of administration to rats showed that the absolute bioavailability after peroral (po), intraduodenal (id), and portal venous (pv) administration is 0.71%, 2.75% and 65.77% respectively for Rb_l, and 3.29%, 6.60% and 50.56% respectively for Rg_l. ConclusionTransport across Caco-2 cell monolayer for PNS (include Rb₁and Rg_l) is a simple passive diffusion process. No efflux transporters in Caco-2 cells and other components in PNS showed effects on it. The elimination in stomach, large intestine and liver contributed to the low bioavailability of PNS, but the low membrane permeability might be a more important factor dominating the extent of absorption.}