Analysis of Transport Mechanism of Flavanomarein in MDCK Monolayer Cell Model

Zheng RAN; Yan-li GUO; Li-feng WANG; Yong-wei ZHANG; Lin-lin LI; Xin LUO; Xin-min MAO

doi:10.13422/j.cnki.syfjx.20190852

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Analysis of Transport Mechanism of Flavanomarein in MDCK Monolayer Cell Model

Pharmacy and Processing | 更新时间：2021-02-09

- Analysis of Transport Mechanism of Flavanomarein in MDCK Monolayer Cell Model
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 15, Pages: 155-160(2019)
- 作者机构：
  
  1.新疆医科大学　省部共建中亚高发病成因与防治国家重点实验室，乌鲁木齐　 830054；
  2.新疆医科大学　基础医学院，中医学院，乌鲁木齐　 830011
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190852
  CLC： R22; R28; R94; Q952; O657.7
- Received：15 November 2018，
  
  Published Online：03 January 2019，
  
  Published：05 August 2019
- 稿件说明：
移动端阅览
Zheng RAN, Yan-li GUO, Li-feng WANG, et al. Analysis of Transport Mechanism of Flavanomarein in MDCK Monolayer Cell Model[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 155-160.
DOI：

Zheng RAN, Yan-li GUO, Li-feng WANG, et al. Analysis of Transport Mechanism of Flavanomarein in MDCK Monolayer Cell Model[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(15): 155-160. DOI： 10.13422/j.cnki.syfjx.20190852.

摘要

目的：

研究黄诺马苷在马丁达比犬肾上皮(MDCK)单层细胞模型上的吸收转运特性。

方法：

利用噻唑蓝(MTT)比色法考察黄诺马苷对MDCK细胞的毒性，使用Millicell-ERS-2型细胞电阻仪检测MDCK单层细胞模型的电阻值，考察黄诺马苷的质量浓度、给药时间以及钠-葡萄糖协同转运蛋白(SGLTs)抑制剂和葡萄糖转运蛋白2(GLUT2)抑制剂对其跨膜转运的影响，采用UPLC-MS/MS测定黄诺马苷的含量，计算表观渗透系数(

app

)及外排比(ER)。

结果：

黄诺马苷质量浓度为5.625～120 mg·L

－1

时对MDCK细胞无明显毒性作用，黄诺马苷在MDCK单层细胞模型上的转运具有时间、浓度依赖性，且

app

基本处于1×10

－6

～10×10

－6

cm·s

－1

。在60 min和90 min时，与空白组相比，根皮苷组中黄诺马苷在MDCK单层细胞模型上的转运量显著减少。

结论：

黄诺马苷在肠道中属于中等吸收的药物，其跨膜转运机制以被动转运为主，兼有主动转运存在，且SGLTs转运体可能参与介导了黄诺马苷在MDCK单层细胞模型上的转运。

Abstract

Objective:

To explore the absorption and transport properties of flavanomarein in the Madin-Darby canine kidney(MDCK) monolayer cell model.

Method:

Methyl thiazolyl tetrazolium(MTT) assay was used to investigate the toxicity of flavanomarein in MDCK cells. The resistance value of MDCK monolayer cell model was detected by Millicell-ERS-2 cell resistometer. The effects of mass concentration of flavanomarein

administration time

sodium-glucose cotransporter(SGLTs) inhibitor and glucose transporter 2(GLUT2) inhibitor on the transmembrane transport of flavanomarein were investigated. The concentration of flavanomarein was determined by UPLC-MS/MS

and the apparent permeability coefficient(

app

) and the efflux ratio(ER) were calculated.

Result:

When the concentration of flavanomarein was 5.625-120 mg·L

-1

there was no significant toxic effect on MDCK cells. The transport of flavanomarein in MDCK monolayer cell model was time-dependent and concentration-dependent. The

app

values of flavanomarein were basically between 1×10

-6

cm·s

-1

to 10×10

-6

cm·s

-1

. Compared with the blank group

the phlorizin group significantly reduced the transport of flavanomarein on the MDCK monolayer cell model at 60 min and 90 min.

Conclusion:

Flavanomarein is a moderately absorbed drug in the intestine

its transmembrane transport mechanism is dominated by passive transport along with active transport. SGLTs may be involved in mediating the transport of flavanomarein on the MDCK monolayer cell model.

关键词

Keywords

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