Transport of Twelve Coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR Cell Monolayer-An in Vitro Model for Blood-Brain Barrier Permeability.
Transport of Twelve Coumarins from Angelicae Pubescentis Radix across a MDCK-pHaMDR Cell Monolayer-An in Vitro Model for Blood-Brain Barrier Permeability.
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DOI：
10.3390/molecules200711719
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发表时间：
2015-06-25
期刊：
影响因子：
--
通讯作者：
Yang XW
中科院分区：
文献类型：
--
作者：
Yang YF;Xu W;Song W;Ye M;Yang XW
独活是一种常用的中药，具有中枢神经系统活性。本研究的目的是表征来自APR的12种香豆素的血脑屏障通透性，包括伞形花内酯（1）、骨化醇（2）、东莨菪内酯（3）、前胡醇（4）、乌普特罗（5）、angepubebisin（6）、补骨脂素（7）、花椒毒素（8）、佛手柑内酯（9）、异欧前胡素（10）、Columbianadin（11）、和醋酸哥伦布胺（12）与使用MDCK-pHaMDR细胞单层的体外模型。经验证，细胞单层适用于渗透实验。采用高效液相色谱法分析了样品的渗透行为，并计算了它们的表观渗透系数（Papp）。根据Papp值，除了4、10和11为中等吸收的化合物外，大多数香豆素类化合物可被表征为吸收良好的化合物，具有浓度依赖性和时间依赖性。P-糖蛋白（P-gp）抑制剂（维拉帕米）实验结果表明，香豆素4的转运受到转运蛋白P-gp的影响。建立了渗透性log（Papp AP-BL*MW0.5）与log D（pH 7.4）之间的S形函数，分析了香豆素类化合物的构效关系。这些结果为揭示APR中枢神经系统活动的物质基础和预测其他香豆素类化合物通过血脑屏障的通透性提供了有用的信息。
Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine, is reported to have central nervous system activities. The purpose of this study was to characterize the blood-brain barrier permeability of twelve coumarins from APR including umbelliferone (1), osthol (2), scopoletin (3), peucedanol (4), ulopterol (5), angepubebisin (6), psoralen (7), xanthotoxin (8), bergapten (9), isoimperatorin (10), columbianadin (11), and columbianetin acetate (12) with an in vitro model using a MDCK-pHaMDR cell monolayer. The cell monolayer was validated to be suitable for the permeation experiments. The samples’ transports were analyzed by high performance liquid chromatography and their apparent permeability coefficients (Papp) were calculated. According to the Papp value, most coumarins could be characterized as well-absorbed compounds except for 4, 10 and 11 which were moderately absorbed ones, in concentration-dependent and time-dependent manners. The results of P-glycoprotein (P-gp) inhibitor (verapamil) experiments showed that the transport of coumarin 4 was affected by the transport protein P-gp. Sigmoid functions between permeability log(Papp AP-BL*MW0.5) and log D (at pH 7.4) were established to analyze the structure-activity relationship of coumarins. The results provide useful information for discovering the substance basis for the central nervous system activities of APR, and predicting the permeability of other coumarins through BBB.
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影响因子：
6.7
作者：
Huong, DTL;Choi, HC;Kim, YH
通讯作者：
Kim, YH
影响因子：
6.7
作者：
Kim, DK;Lim, JP;Leem, KH
通讯作者：
Leem, KH
影响因子：
1.7
作者：
Yang, Xiu-Wei;Zhang, Cai-Yu;Zheng, Qi-Tai
通讯作者：
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影响因子：
2.7
作者：
Madgula, Vamsi L. M.;Avula, Bharathi;Khan, Shabana I.
通讯作者：
Khan, Shabana I.
DOI：
10.1034/j.1600-0773.2001.d01-86.x
发表时间：
2001-02-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
Kong, LD;Tan, RX;Cheng, CHK
通讯作者：
Cheng, CHK