ABSTRACT
The absorption is the key to the resulted efficacy of orally administered drugs and the small intestine is the main site to absorb the orally administered drug. In this paper, internationally recognized human colon adenocarcinoma cell line(Caco-2) monola-yer model which can simulate small intestinal epithelial cell was used to comparatively study the absorption and transportation diffe-rences of total coumarins and main individual coumarin in Angelica dahurica 'Yubaizhi' by separately using 6-and 12-well plates. It was found that apparent permeability coefficient(P_(app)) values of oxypeucedanin hydrate, byakangelicin and phellopterin were at the quantitative degree of 1 × 10~(-5) cm·s~(-1) when the individual administration was conducted independently, indicating that they were well-absorbed compounds. P_(app) ratio of their bi-directional transportation was close to 1, indicating that they can be absorbed across Caco-2 monolayer by passive diffusion mechanism without carrier mediation during the transportation. The similar trend of transportation was also observed for imperatorin, isoimperatorin and bergapten. The P_(app) values of oxypeucedanin hydrate, byakangelicin and bergapten were at quantitative degree of 1 × 10~(-5) cm·s~(-1) when the administration of total coumarins in Angelica dahurica 'Yubaizhi' was conducted, indicating that they were well-absorbed compounds. The results were consistent with those of independent administration of individual coumarins. Whereas, the P_(app) values of imperatorin, phellopterin and isoimperatorin in the total coumarins decreased, indicating that the interaction between compounds may exist although the P_(app) value ratio of bi-directional transportation was between 0.5 and 1.5. The results laid the foundation for intestinal absorption study of Angelica dahurica 'Yubaizhi' coumarins in compound Chinese medicine.
Subject(s)
Humans , Angelica , Caco-2 Cells , Coumarins , Drugs, Chinese Herbal , Intestinal Absorption , Plant RootsABSTRACT
Objective: To evaluate the effect of low molecular weight chitosan (LMW-CTS) and its nanoparticles (LMW-CTS-NPs) on the intestinal permeability of Panax notoginseng saponins (PNS) by using Caco-2 cell model. Methods: LMW-CTS was prepared by combining chitosanase hydrolysis combined with ultrafiltration separation technology, and molecular weight of LMW-CTS was determined by using permeation gel chromatography (GPC). LMW-CTS-NPs were prepared by ionic gel method, and characterized by scanning electron microscopy, nano particle sizer, and flourier transformation infrared spectroscopy. Caco-2 cell model was established and validated to evaluate the effects of LMW-CTS and LMW-CTS-NPs on the intestinal permeability of PNS. Results: LMW-CTS has a molecular weight of 5 760 and a polydispersity coefficient of 1.42. LMW-CTS-NPs have a round shape and narrow particle size distribution, with an average particle size of 115.5 nm and zeta potential of +37.1 mV. The apparent permeability coefficients (Papp, AB→BL) of PNS was less than 1 × 10-6 cm/s, indicating a poor permeability. In LMW-CTS group, the Papp of R1 and Rg1 was increased by 17.83% and 20.29%, respectively, but no significant effect of promotion was observed on other components. However, the Papp of R1, Rg1, Re, Rb1, and Rd in LMW-CTS-NPs group was increased by 35.66%, 23.28%, 29.41%, 37.99%, and 36.00%, respectively, compared tothe control group. Conclusion: LMW-CTS can significantly promote the intestinal mucosal permeability of R1 and Rg1 in PNS, but has no significant effect on Re, Rb1, and Rd. LMW-CTS-NPs significantly increased the permeability of the major monomer saponin components in PNS. Namely, the intestinal permeability of PNS can be further improved by transforming LMW-CTS into LMW-CTS-NPs.
ABSTRACT
Objective: Meglucumin cocrystal (MGC) is a new cocrystal compound which consists of curcumin with meglumine by hydrogen bond. The intestinal absorption parameter changes of MGC would be observed and be compared with curcumin. Methods: The intestine in rats was cannulated for in situ perfusion to study the absorption mechanism of MGC; UV was used to determine the concentration of MGC, to calculate the order of the absorption rate constants (Ka), and apparent permeability coefficients (Papp). Results: The Ka and Papp of MGC in the duodenum has significantly increased compared with the colon (P0.05) in other isolated regions of the intestine. The order was: duodenum>jejunum>ileum>colon; And that of Papp was: duodenum>jejunum>colon>ileum. The Ka and Papp in the whole intestine were (9.966±0.030)×10-3 min-1and (6.871±0.013)×10-3 cm/min respectively for the MGC which were 1.53 times and 2.21 times higher than these of curcumin. Conclusion: MGC is a better intestinal absorption characteristic than these of curcumin, suggesting that the bioavailability of MGC may be increased.
ABSTRACT
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.
ABSTRACT
Objective: To study the absorption and transport characteristic of paeoniflorin (PF), oxypaeoniflorin (OP), benzoylpaeoniflorin (BP), tetraacetylpaeoniflorin (TP), pentaacetylpaeoniflorin (PP), and pentacacetylalbiflorin (PA) in human colon adenocarcinoma cell line Caco-2 cell monolayer model. Methods: The Caco-2 cell monolayers were used as an intestinal epithelial cell model. The permeability of the tested compounds from apical (AP) side to basolateral (BL) side or from BL side to AP side was evaluated. The concentration of the tested compounds was measured by HPLC coupled with UV detector. The transport parameters and apparent permeability coefficients (Papp) were calculated, and the Papp values were compared with the reported values for model compounds, Propranolol and Atenolol. Results: The Papp values of PF in the bi-directional transport and atenolol were at the quantitative degree of 10-7 cm/s. Whereas those of OP, BP, TP, PP, and PA were between atenolol and propranolol used as a control substance for low and high permeability, respectively. The absorption and transport of the tested compounds were concentration-dependent at the concentration range of 10-200 μmol/L for PF, OP, and BP, 10-150 μmol/L for TP and PA, and 10-100 μmol/L for PP. Conclusion: The six tested compounds could be absorbed across the intestinal epithelial cells by passive diffusion mechanism. PF is poorly absorbed compound and OP, BP, TP, PP, and PA are moderately absorbed compounds. BP has a role to promote atenolol uptake transporters in Caco-2 cell monolayer model.