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首页> 外文期刊>Molecules >Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model
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Elucidation of Transport Mechanism of Paeoniflorin and the Influence of Ligustilide, Senkyunolide I and Senkyunolide A on Paeoniflorin Transport through Mdck-Mdr1 Cells as Blood-Brain Barrier in Vitro Model

机译：Pa药苷的转运机制及and本内酯，Senkyunolide I和Senkyunolide A对通过Mdck-Mdr1细胞作为血脑屏障的Pa药苷转运体外模型的影响

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The objectives of the present investigation were to: (1) elucidate the transport mechanism of paeoniflorin (PF) across MDCK-MDR1 monolayers; and (2) evaluate the effect of ligustilide (LIG), senkyunolide I (SENI) and senkyunolide A (SENA) on the transport of PF through blood-brain barrier so as to explore the enhancement mechanism. Transport studies of PF were performed in both directions, from apical to basolateral side (AB) and from basolateral to apical sides (BA). Drug concentrations were analyzed by LC-MS/MS. PF showed relatively poor absorption in MDCK-MDR1 cells, apparent permeability coefficients (Papp) ranging from 0.587 x 10(-6) to 0.705 x 10(-6) cm/s. In vitro experiments showed that the transport of PF in both directions was concentration dependent and not saturable. The BA/AB permeability ER of PF was more than 2 in the MDCK-MDR1 cells, which indicated that the transport mechanism of PF might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased Papp of PF in AB direction by EDTA-Na-2 suggested that PF was absorbed via the paracellular route. The P-gp inhibitor verapamil could significantly increase the transport of PF in AB direction, and ER decreased from 2.210 to 0.690, which indicated that PF was P-gp substance. The transport of PF in AB direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. An increased cellular accumulation of Rho 123 and Western blot analysis indicated that LIG, SENI and SENA had increased the transport of PF in the BBB models attribute to down-regulate P-gp expression. A decrease in transepithelial electrical resistance (TEER) during the permeation experiment can be explained by the modulation and opening of the tight junctions caused by the permeation enhancer LIG, SENI and SENA.
机译：本研究的目的是：（1）阐明of药苷（PF）跨MDCK-MDR1单层的转运机制; （2）评估li本内酯（LIG），千古油化物I（SENI）和千古油化物A（SENA）对PF通过血脑屏障的转运的作用，以探讨其增强机制。从根尖到基底外侧（AB）和从基底外侧到根尖（BA）的两个方向都进行了PF的转运研究。通过LC-MS / MS分析药物浓度。 PF在MDCK-MDR1细胞中显示出相对较差的吸收，表观渗透系数（Papp）从0.587 x 10（-6）到0.705 x 10（-6）cm / s。体外实验表明，PF在两个方向上的运输都与浓度有关，并且不饱和。在MDCK-MDR1细胞中，PF的BA / AB渗透率ER大于2，这表明PF的转运机制可能是被动扩散，而主动转运介导的机制是其主要过程。 EDTA-Na-2使PF在AB方向上的Papp增加，表明PF通过细胞旁途径吸收。 P-gp抑制剂维拉帕米可显着增加PF在AB方向上的转运，而ER从2.210降至0.690，表明PF是P-gp物质。与浓度增加的LIG，SENI和SENA并用时，PF沿AB方向的转运显着增加。 Rho 123细胞积累的增加和蛋白质印迹分析表明，LIG，SENI和SENA在BBB模型中增加了PF的转运，这归因于下调P-gp表达。渗透实验过程中跨上皮电阻（TEER）的降低可以通过渗透增强剂LIG，SENI和SENA引起的紧密连接的调节和打开来解释。

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