Aim:To clarify the cause of poor oral absorption of ginsenoside Rg_1(Rg_1),theactive ingredient in Panax notoginseng saponins(PNS)used for treatinghemorrhage.Methods:Caco-2 cell monolayers were used as an in vitro model tostudy the transport mechanism of Rg_1 across the intestinal mucosa.Moreover,the serum concentration-time profiles after peroral(po),intraduodenal(id),portalvenous(pv)and tail venous(iv)administration of Rg_1 in rats were compared toevaluate 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 notinfluenced by cyclosporin A.The change in the apical pH produced no obviouseffect 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,indicatingpassive 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 ob-served 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 thebarrier function of the intestine was more significant than those of the stomachand liver in the absorption process.Conclusion:Elimination in the stomach,largeintestine and liver contributed to the low oral bioavailability of Rg_1,but low mem-brane permeability might be a more important factor in determining the extent ofabsorption. 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 treatinghemorrhage.Methods:Caco-2 cell monolayers were used as an in vitro model tostudy the transport mechanism of Rg_1 Across the intestinal mucosa.Moreover,the serum concentration-time profiles after peroral(po),intraduodenal(id),portalvenous(pv)and tail venous(iv)administration of Rg_1 in rats were compared toevaluate 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 notinfluenced 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(AB) increased in an linear manner with the increase in concentration,indicatingpassive 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 ob-served 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,largeintestine And liver contributed to the low oral bioavailability of Rg_1,but low mem-brane permeability might be more important factor in determining the extent of absorption.