Transport of decursin and decursinol angelate across Caco-2 and MDR-MDCK cell monolayers:: In vitro models for intestinal and blood-brain barrier permeability
Transport of decursin and decursinol angelate across Caco-2 and MDR-MDCK cell monolayers:: In vitro models for intestinal and blood-brain barrier permeability
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DOI：
10.1055/s-2007-967137
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发表时间：
2007-04-01
期刊：
影响因子：
2.7
通讯作者：
Khan, Shabana I.
中科院分区：
文献类型：
--
作者：
Madgula, Vamsi L. M.;Avula, Bharathi;Khan, Shabana I.
从伞形科植物当归（Angelica gigas）的根中分离得到两个新化合物Decursin（DE）和decursinol angelate（DA）。据报道，DE和DA表现出显著的神经药理学活性，但它们在CNS穿透血脑屏障（BBB）方面的肠转运和渗透性尚不清楚。本研究分别使用Caco-2和MDR-MDCK细胞单层模型评价DE和DA的体外肠和BBB转运。检查DE和DA跨Caco-2和MDR-MDCK单层的双向转运2小时。通过TEER值和通过监测荧光黄（Ly）跨单层的转运来确定单层的完整性。通过HPLC进行DE和DA的定量。DE和DA在Caco-2和MDR-MDCK单层中表现出双向转运，Papp值范围分别为9.0 - 12.0 x 10（-6）cm/sec和7.2 - 11.7 x 10（-6）cm/sec。Caco-2和MDR-MDCK单层的TEER值分别在410 - 440和1170 - 1230 ohm cm（2）范围内。Ly测量（被动细胞旁扩散的荧光标记物）导致Caco-2中Papp值为2.5 - 5.0 x 10（-6）cm/ sec，MDR-MDCK单层中Papp值为6.0 - 8.0 x 10（-6）cm/ sec，证实实验结束时单层完整性完好。
Decursin (DE) and decursinol angelate (DA) were isolated from the roots of Angelica gigas (Apiaceae) and purified by HPLC. DE and DA have been reported to exhibit significant neuropharmacological activities, but their intestinal transport and permeability in terms of CNS penetration across the blood-brain barrier (BBB) are unknown. This study was undertaken to evaluate the in vitro intestinal and BBB transport of DE and DA using Caco-2 and MDR-MDCK cell monolayer models, respectively. The bidirectional transport of DE and DA across Caco-2 and MDR-MDCK monolayers was examined for 2 hours. Integrity of the monolayer was determined by TEER value and by monitoring the transport of Lucifer yellow (Ly) across the monolayers. Quantitation of DE and DA was performed by HPLC. DE and DA exhibited bidirectional transport with a Papp value in the range of 9.0 - 12.0 x 10(-6) cm/sec and 7.2 - 11.7 x 10(-6) cm/sec in Caco-2 and MDR-MDCK monolayers, respectively. The TEER values were in the range of 410 - 440 and 1170 - 1230 ohm cm(2) for Caco-2 and MDR-MDCK monolayers, respectively. Ly measurement, the fluorescent marker of passive paracellular diffusion, resulted in Papp values of 2.5 - 5.0 x 10(-6) in Caco-2 and 6.0 - 8.0 x 10(-6) cm/ sec in MDR-MDCK monolayers, confirming that the monolayer integrity was intact at the end of the experiment.