Absorptive characteristic of Bletilla striata extract in Caco-2 cell monolayer / 中国中药杂志

To investigate the active fraction from Bletilla striata in Caco-2 cell monolayer,so as to explore its absorption mechanism of oral administration preliminarily.Active fraction from B.striata in Caco-2 cell monolayer was analyzed by UPLC-Q-TOF and detected by UPLC-MS/MS,and the effects of different concentrations,pH and P-glycoprotein inhibitors on Caco-2 cells Monolayer were investigated.Six compounds were isolated from the active fraction of B.striata in Caco-2 cell monolayer by UPLC-Q-TOF,and identified as B6,B12,B14,B17,B19 and B23,with concentration dependence.Within the 0-180 min,the uptake of B12 and B14 had a time dependence,while B6,B17,B19 and B23 tended to saturate after 60 min.All of the components had a good absorption in an acidic environment.B6 had a good absorption at pH 6.0,while the other components B12,B14,B17,B19 and B23 had a good absorption at pH4.0.The absorption of the 6 main components of B.striata were not be affected by P-glycoprotein inhibitors(verapamil/cyclosporin A).Compared with the control group,there was no difference in the absorption of B6 and B12,and the absorption of B14,B17,B19 and B23 increased,but with no significant difference.The absorption characteristic of B.striata extract across the Caco-2 cell monolayer is probably passive diffusion,and the absorption process was not affected by P-glycoprotein.

Absorption characteristics of 5 components of Xinshao extract in Caco-2 cells / 中国中药杂志

To study the absorption characteristics of Xinshao extracts in Caco-2 cells. In this paper, human colon adenocarcinoma cell line Caco-2 cell model was established, and UPLC-MS method was applied to determinate the contents of five components of Xinshao extracts(albiflorin, gallic acid, caffeic acid, scutellarin and apigenin-7-O-glucronide) in cell lysates. This model was also used to study the effect of different drug concentrations, pH, time and temperature on the absorption of five components, investigate the transport of the five components of Xinshao extracts under the conditions with or without P-glycoprotein inhibitors, and predict the absorption mechanism of these five components in Caco-2 cells. The experimental results showed that the absorption of five components of Xinshao extracts in Caco-2 cells was time-dependent at 37 ℃, and concentration-dependent in the range of 0.5-12.5 g•L⁻¹, with a passive diffusion mechanism. At the pH of 4-7.4, the absorption of caffeic acid, scutellarin and apigenin-7-O-glucronide was significantly declined with the increase of pH(P<0.05). At the temperature of 4 to 37 ℃, the absorption of caffeic acid was declined with the increase of temperature, while the absorption of other four components was increased with the increase of temperature. Compared with the control group, caffeic acid and scutellarin cell absorption was significantly higher(P<0.05) after treatment with P-glycoprotein inhibitors(verapamil and cyclosporine A). The results indicated that, the absorption mechanism of five components in Xinshao extracts may be of passive diffusion, and the caffeic acid and scutellarin may be the substrates of P-glycoprotein.

Transportation of 8-isopropylaminomethyl hesperitin(IPHP) across human intestinal epithelial by using Caco-2 cells / 中国药理学通报

Aim To study the mechanism of 8-isopro-pylaminomethyl hesperitin ( IPHP ) intestinal absorp-tion using Caco-2 cell lines. Methods Using Caco-2 cell lines as an intestinal epithelial cell model, the effects of drug concentration, temperature, pH, P-gly-coprotein ( P-gp) inhibitor verapamil and multidrug re-sistance protein 2 ( MRP2 ) inhibitors MK-571 or pro-benecid on IPHP transport across Caco-2 cell lines were all investigated. Results The transportation of IPHP was related to drug concentration. The Papp ( AP-BL) ( × 10 -5) was (2. 21 ± 0. 200) cm·s-1,(3. 56 ± 0. 306) cm·s-1,(3. 81 ± 0. 179) cm·s-1,(4. 23 ± 0. 229 ) cm · s-1 , ( 4. 17 ± 0. 262 ) cm · s-1 , re-spectively, and Papp(BL-AP) ( × 10 -5) was (3. 57 ±0. 209) cm·s-1,(4. 51 ± 0. 113) cm·s-1,(4. 97 ± 0. 229) cm·s-1,(5. 24 ± 0. 550) cm·s-1,(5. 07 ± 0. 557) cm·s-1,respectively. Efflux rate was 1. 61, 1. 26,1. 3,1. 23,1. 21,respectively. Temperature and pH both influenced the transport, While the P-gp in-hibitor verapamil had no effect on the transport of IPHP. MRP2 inhibitors MK-571 or probenecid led to an apparent decrease in the efflux of IPHP. Conclu-sion The results suggest that the transport of IPHP is mainly passive diffusion, and MRP2 but not P-gp may be involved in the transport of IPHP.

In vivo intestinal absorption characteristics of α-hederin in rats / 中草药

Objective: To investigate the intestinal absorption characteristics of α-hederin and to explore the causes of poor bioavailability. Methods: In vivo single-pass perfusion model was used and the concentration of α-hederin was determined by HPLC. The effects of intestinal segment, drug concentration, pH value, gut microflora, and P-gp inhibitor on the intestinal absorption of the drug were investigated. Results: The absorption rate constant (Ka) of α-hederin decreased following the sequence of ileum > colon > jejunum > duodenum. Absorption parameters of α-hederin had no significant difference at different concentration of 75, 150, and 300 μg/mL and those increased with the increase of pH value. The intestinal flora which were disrupted may affect the absorption of α-hederin. There was no significant difference in Ka and Peff values between P-gp inhibitor and no P-gp inhibitor groups. Conclusion: α-Hederin can be absorbed in whole intestine, but better in lower intestine. The saturate phenomena was not observed under the test range of drug concentration, and the absorption mechanism may be the passive diffusion transport. The absorption can be better under basic condition. The absorption is significantly affected by the intestinal flora and α-hederin is not the substrate of P-gp.

Transport characteristics of hydroxysafflor yellow A across Caco-2 cell monolayer model / 中草药

Objective: To investigate the transport characteristics of hydroxysafflor yellow A (HSYA) in Danhong Injection across Caco-2 cell monolayer. Methods: Safe concentration range of HSYA against Caco-2 cell monolayer model was selected by MTT method; The effects of time, drug concentration, temperature, pH, P-gp inhibitor (Verapamil), and energy metabolism inhibitor (sodium azide) on the absorption of HSYA were observed by Caco-2 cell monolayer model; The multidrug resistance (MDR1) gene expression in Caco-2 cells was analyzed by the RT-PCR method. Results: The Papp of HSYA transport from apical (AP) side to basolateral (BL) side was in 2 × 10-6-5 × 10-6 cm/s, which showed a medium absorption. The transport of HSYA was positively correlated with time and concentration. The Papp of HSYA transport at 37°C has significant differences with those at 4 and 25°C (P < 0.01). The Papp of HSYA transport under pH 9.0 has significant differences with those under pH 5.0 and 7.4 (P < 0.01). The gene expression of MDR1 was significantly reduced by Verapamil, but the transport of HSYA was not influenced by Verapamil and sodium azide, the number of Papp(BL→AP)/Papp(AP→BL) was between 1 and 1.5, so the absorption of HSYA was basically in line with the passive diffusion. Conclusion: The transport of HSYA across Caco-2 cell monolayer model is passive diffusion, and is not influenced by the change of P-gp and energy metabolism. Low temperature and alkaline environment are not conducive to the absorption of HSYA.

Absorption mechamism of dehydroandrographolide in human caco-2 cell monolayer model / 中草药

Objective: To study the absorption mechanism of dehydroandrographolide (DAL) in human Caco-2 cell monolayer model. Methods: Caco-2 cell monolayer model was applied to investigate the bidirectional transport of DAL. The effects of time, drug concentration, temperature, and P-gp inhibitor (Verapamil) on the absorption of DAL were observed. Drug concentration was measured by LC/MS/MS and the apparent permeability coefficients (Papp) were calculated. Results: With the time and concentration increasing, the bidirection transport of DAL in Caco-2 cell monolayer model was of time and concentration dependence, without saturation. And it was not influenced by the change of temperature and the presence of Verapamil. Conclusion: The absorption and transport of DAL are passive diffusion as the dominating process in Caco-2 cell monolayer model.

Small intestinal absorption manners of glimepiride in rats / 第三军医大学学报

Objective To study the small intestinal absorption patterns of glimepiride in rats. Methods A rat model of small intestinal absorption in vivo was employed in this study. The small intestinal absorption rate of glimepiride was detected by high performance liquid chromatography. Results At the low and high concentrations of glimepiride, the average small intestinal absorption rates were 0.233 6 h -1 and 0.217 8 h -1 , respectively. Conclusion The small intestinal absorption pattern of glimepiride might be passive diffusion.