Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp

Wang, Xiaodan; Meng, Minxin; Gao, Lingbo; Liu, Ting; Xu, Qiang; Zeng, Su

doi:10.1016/j.ijpharm.2009.05.022

Cited by 63 publications

(58 citation statements)

References 33 publications

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“…The human colon adenocarcinoma cell line (Caco-2) is now routinely cultivated as monolayers on permeable filters for the transepithelial transport of drugs [3] , and this model has been used extensively to screen the absorptive capability and capacity of a variety of nutrients and pharmaceuticals [4][5][6] . However, one of the functional differences between normal cells and Caco-2 cells is the lack of expression of the cytochrome P450 isoenzymes, particularly CYP3A4, as well as some uridine diphosphate-glucuronosyltransferases (UGTs), such as UGT1A1 [7] .…”

Section: Introductionmentioning

confidence: 99%

Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

Wang

Shan

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the mechanisms underlying the intestinal absorption of the major bioactive component forsythoside A (FTA) extracted from Forsythiae fructus. Methods: An in vitro Caco-2 cell model and a single-pass intestinal perfusion in situ model in SD rats were used. Results: In the in vitro Caco-2 cell model, the mean apparent permeability value (P app -value) was 4.15×10 -7 cm/s in the apical-tobasolateral (AP-BL) direction. At the concentrations of 2.6-10.4 μg/mL, the effl ux ratio of FTA in the bi-directional transport experiments was approximately 1.00. After the transport, >96% of the apically loaded FTA was retained on the apical side, while >97% of the basolaterally loaded FTA was retained on the basolateral side. The P app -values of FTA were inversely correlated with the transepithelial electrical resistance. The paracellular permeability enhancers sodium caprate and EDTA, the P-gp inhibitor verapamil and the multidrug resistance related protein (MRP) inhibitors cyclosporine and MK571 could concentration-dependently increase the Papp-values, while the uptake (OATP) transporter inhibitors diclofenac sodium and indomethacin could concentration-dependently decrease the P app -values. The intake transporter SGLT1 inhibitor mannitol did not cause signifi cant change in the P app -values. In the in situ intestinal perfusion model, both the absorption rate constant (K a ) and the effective permeability (P eff -values) following perfusion of FTA 2.6, 5.2, and 10.4 μg/mL via the duodenum, jejunum and ileum had no signifi cant difference, although the values were slightly higher for the duodenum as compared to those in the jejunum and ileum. The low, medium and high concentrations of verapamil caused the largest increase in the P eff -values for duodenum, jejunum and ileum, respectively. Sodium caprate, EDTA and cyclosporine resulted in concentration-dependent increase in the P eff -values. Diclofenac sodium and indomethacin caused concentration-dependent decrease in the Peff-values. Mannitol did not cause signifi cant change in the P app -values for the duodenum, jejunum or ileum. Conclusion:The results suggest that the intestinal absorption of FTA may occur through passive diffusion, and the predominant absorption site may be in the upper part of small intestine. Paracellular transport route is also involved. P-gp, MRPs and OATP may participate in the absorption of FTA in the intestine. The low permeability of FTA contributes to its low oral bioavailability.

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Section: Introductionmentioning

confidence: 99%

Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

Wang

Shan

et al. 2012

Acta Pharmacol Sin

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“…P app values of CAPE and CAPE-NO 2 exceeded 10 À6 cm/s, implying a relatively high intestinal permeability in vivo (Yee 1997). It has been reported that the P app values of taxifolin, caffeic acid, ferulic acid and isoliquirtigenin were less than 10 À6 , (1.4 ± 0.1) Â 10 À6 , (10 ± 0.2) Â 10 À6 and (11.77 ± 3.14) Â 10 À6 , respectively, and the lipophilicity and the membrane permeability coefficient of these compounds increased with the numbers of hydroxyl groups decreasing (Wang et al 2009a;Farrell et al 2012;Yang et al 2014). CAPE and CAPE-NO 2 are structurally similar with these above polyphenoliclike substances, and the P app value of CAPE-NO 2 (12.34 ± 1.6 Â 10 À6 ) was 2-to 4-fold higher than CAPE Figure 5.…”

Section: Discussionmentioning

confidence: 95%

“…It is the main efflux pump for a variety of chemicals, which play the important roles in the absorption and distribution of many polyphenolic compounds (Wang et al 2009a;Hong et al 2015). Some polyphenolic compounds have demonstrated the ability to up-regulate or inhibit the function of P-gp (Kitagawa 2006;Chieli et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Absorption properties and effects of caffeic acid phenethyl ester and its p-nitro-derivative on P-glycoprotein in Caco-2 cells and rats

Gou

Xiao

Tang

et al. 2016

Pharmaceutical Biology

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Context: Caffeic acid phenethyl ester (CAPE), isolated from honeybee propolis, has pharmacological applications. A synthesized CAPE derivative, p-nitro-caffeic acid phenethyl ester (CAPE-NO 2 ), showed similar activities with CAPE. The pharmacological activities of CAPE and CAPE-NO 2 are related to their absorption properties. Objective: To understand the pharmacokinetic profiles of CAPE and CAPE-NO 2 in rats and investigate the absorption mechanisms and effects on P-glycoprotein in Caco-2 cells. Materials and methods: The pharmacokinetic profiles of CAPE and CAPE-NO 2 were obtained after oral administration (10 mg/kg) to rats. Transport studies of CAPE and CAPE-NO 2 (5, 10, 20 lM) were performed in Caco-2 cell model. P-gp activities were assayed by rhodamine 123 cellular retention. Expression of P-gp was determined after the cells were administrated with CAPE and CAPE-NO 2 (5, 20 lM) for 48 and 72 h. Results: The AUC (0Àt) of CAPE-NO 2 (3239.9 ± 352 ng Â h/mL) was two-time greater than CAPE (1659.6 ± 152 ng Â h/mL) in rats. The P app values of CAPE and CAPE-NO 2 were (4.86 ± 0.90) Â 10 À6

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“…β-Actin was the internal standard and was detected using rabbit polyclonal anti-β-actin as primary antibody and HRP-conjugated goat anti-rabbit IgG as secondary antibody. P-gp expression is presented as the ratio of P-gp band intensity to β-actin band intensity in the same blot run (P-gp/β-actin) (Wanga et al, 2009). …”

Section: Western Blotting Analysis Of P-gp Expressionmentioning

confidence: 99%

“…The mobile phase was pumped in isocratic mode at a flow rate of 2 mL/min at ambient temperature. UV detection was performed at 218 nm, and the injection volume of samples was 20 L. The HPLC column was Knauer-15VE081ESJ-150X 4.6 mm with precolumn-Eurospher 100-5 C8 (Wanga et al, 2009). …”

Section: Hplc Analysis Of Digoxin In Perfused Samplesmentioning

confidence: 99%

In vitro and in situ effects of atorvastatin and ezetimibe on P-glycoprotein expression and function

Abbasi¹,

Valizadeh²,

Hamishehkar³

et al. 2016

Bangladesh J Pharmacol

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P-glycoprotein (P-gp) is a membrane transporter responsible for the active efflux from the cell. Inhibition of the activity may lead to clinically significant drug-drug interactions. This study was performed to investigate the effects of atorvastatin and ezetimibe on the function and expression of P-gp. The in vitro rhodamine-123 (Rho123) efflux assay and Western blot in Caco-2 cells, and the in situ rat single-pass intestinal permeability model followed by high performance liquid chromatography were developed. Rho123 intracellular accumulation in 100 µM of atorvastatin- and ezetimibe-treated cells was significantly higher than that in control cells (p<0.05). P-gp expression was decreased by 100 µM atorvastatin and ezetimibe. Intestinal effective permeability of digoxin in the presence of atorvastatin (3 and 100 µM), ezetimibe (10 and 100 µM) was significantly increased (p<0.05). Both drugs inhibited P-gp activity in vitro and in situ. Atorvastatin and ezetimibe down-regulated the expression of P-gp in vitro. Video Clip of Methodology:<a href="https://youtube.com/v/BQuz1ER3_NQ">Single-pass intestinal permeability</a>: 17 min 26 sec

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Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp

Cited by 63 publications

References 33 publications

Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

Intestinal absorption of forsythoside A in in situ single-pass intestinal perfusion and in vitro Caco-2 cell models

Absorption properties and effects of caffeic acid phenethyl ester and its p-nitro-derivative on P-glycoprotein in Caco-2 cells and rats

<i>In vitro</i> and <i>in situ</i> effects of atorvastatin and ezetimibe on P-glycoprotein expression and function

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