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Objective:To investigate the transport mechanism of punicalagin in MDCK monolayer model .Methods:The safe con-centration of punicalagin in MDCK cells was determined by CCK8 assay.Millicell -ERS was used to measure cell monolayer TEER value to determine the integrity of the cell monolayer .The effects of direction , drug concentration , time, P-gp inhibitor and EDTA-Na2 on the absorption and transport of punicalagin were studied systematically .And then the drug concentration was analyzed by HPLC to calculate the apparent permeability coefficient (Papp) and efflux ratio(ER).Results: Punicalagin transport in MDCK cells was time and concentration dependent .Punicalagin showed poor absorption in MDCK cells .Papp from apical to basolateral side ( AP-BL) within the concentration range of 100-300μg· ml-1 was (6.13 ±0.12) ×10 -7 cm· s-1 , (6.96 ±0.26) ×10 -7 cm· s-1 and (5.94 ±0.10) ×10 -7 cm· s-1 , respectively .P-gp inhibitor and EDTA-Na2 could significantly increase the transport of punicalagin in AP-BL direc-tion, while the transport decreased at 4℃.Conclusion:The transport mechanism of punicalagin might be passive diffusion as the dom-inating process involving active transportation .Punicalagin is one of P-gp substrates with exocytosis and absorbed via the paracellular route.
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Aim To study the transport of geniposide and geniposide in Zhizi Bopi Decoction in MDCK cell membrane model. Methods The safety concentration of geniposide and Zhizi Bopi Decoction in MDCK cells were determined by MTT assay. Then the MDCK cell membrane model was used to investigate the transport of drugs. Firstly, the effects of time, drug concentra-tion, P-gp inhibitor and EDTA on the absorption and transport of geniposide were studied systematically. Secondly, the differences were compared between the transport of the same concentration of geniposide as single compound and that in Zhizi Bopi Decoction in MDCK cell model. The drug concentration was deter-mined by high performance liquid chromatography ( HPLC) to calculate the apparent permeability coeffi-cient (Papp). Results Geniposide transport in MDCK cell monolayer was time and concentration dependent. P-gp inhibitors had no significant effect on its transport and the transport of geniposide was enhanced by ED-TA. The absorption Papp of different concentrations of geniposide in Zhizi Bopi Decoction were ( 8. 96 ± 0. 35 ) × 10 -7 cm · s-1 , ( 8. 95 ± 0. 38 ) × 10 -7 cm · s-1 and (9. 16 ± 0. 30) × 10 -7 cm·s-1, significantly higher than the absorption Papp of geniposide as single compound(5. 85 ± 0. 44) × 10 -7 cm·s-1, (6. 88 ± 0. 38) × 10 -7 cm·s-1 and (6. 31 ± 0. 19) × 10 -7 cm ·s-1 ( P<0. 05 ) . Conclusion The transport of ge-niposide in MDCK cell membrane model is passive transport and is not affected by P-gp. Geniposide may transport via the paracellular route. The Zhizi Bopi De-coction can increase the absorption of geniposide.
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Objective: To investigate the transport characteristics of ligustrazine across Caco-2 cell monolayer and the effect on P-glycoprotein (P-gp) expression. Methods: Safe concentration range of ligustrazine against Caco-2 cell monolayer model was selected by the MTT method. The mechanism of ligustrazine bidirectional transport was investigated by Caco-2 cell monolayer model. The influences of time, concentration, and P-gp inhibitor Verapamil on the transport of ligustrazine were studied using apparent permeability coefficient (Papp) as index. P-gp expression in Caco-2 cells was analyzed by the Western blotting method. Results: The Papp of transport from apical (AP) side to basolateral (BL) side was over 10-6 cm/s, which showed a good absorption. In the Caco-2 cell model, the transport amount of ligustrazine was positively correlated with time and concentration, and the transport amount from AP side to BL side was higher than that from BL to AP. The absorption of ligustrazine was not only rejected by P-gp, but also the P-gp expression was inhibited by ligustrazine. Conclusion: The transport of ligustrazine across Caco-2 cell monolayer model is deduced as passive transport, ligustrazine is rejected by P-gp, and there is an inhibition of ligustrazine on the expression of P-gp.
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Objective: To investigate the in vivo absorptive characteristic of arctiin in small intestine of rats. Methods: The intestine absorption model of arctiin was established by in vivo intestinal perfusion method. The absorption rate constants (Ka), absorption half time (t1/2), absorption percent of per unit of time (P), and apparent permeability coefficient (Papp) were calculated and compared to investigate the absorptive dynamics of arctiin in intestine of rats. Results: At the concentration range of 10-50 μg/mL, Ka, t1/2, P, and Papp showed no significant difference, and had no connection with concentration of arctiin. Conclusion: Arctiin complies with the first-order absorptive kinetics and the absorptive mechanism in intestine may be passive transport.