The blood-brain barrier permeability of 20(S) and 20(R)-protopanaxatriol epimers and dammar-20(22)E,24-diene-3β,6α,12β-triol in MDCK-pHa MDR cell monolayer model  

20(S)-原人参三醇和20(R)-原人参三醇差向异构体及达玛-20(22)E,24-二烯-3β,6α,12β-三醇在MDCK-pHaMDR细胞单层模型中的跨血脑屏障研究（英文）

作　　者：郑怡然 吴秀稳 杨秀伟 

机构地区：[1]北京大学医学部药学院天然药物学系天然药物及仿生药物国家重点实验室,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2017年第8期566-573,共8页中国药学（英文版）

基　　金：The National New Drug R&D Program(Grant No.2011BAI07B08;2009ZX09301-010)of China

摘　　要：The blood-brain barrier permeability of 20（S） and 20（R）-protopanaxatriol epimers and dammar-20（22）E,24-diene- 313,6α,12β-triol were investigated using the MDCK-pHaMDR cell monolayer model. The bidirectional permeability tests were carried out, and the apparent permeability coefficients （Papp） were calculated. The two protopanaxatriol epimers showed good permeability with Papp values of-10^-5 cm/s, whereas dammar-20（22）E,24-diene-3β,6α, 12β-triol showed poor permeability with Papp of 〈1 × 10^-7 cm/s. The three compounds showed differences in intracellular accumulations due to their different structures. Inhibition of P-gp with verapamil showed that the transport mechanisms in MDCK-pHaMDR cell monolayer for compounds 1 and 2 epimers were not only simple passive diffusion but also involving an effiux way mediated by P-gp. These findings provided new basis for the further study of compounds 1 and 2 acting on the brain.本文应用MDCK-p Ha MDR细胞单层模型,评价20(S)-原人参三醇(1)和20(R)-原人参三醇(2)差向异构体及达玛-20(22)E,24-二烯-3β,6α,12β-三醇(3)在血脑屏障的吸收性。为了评价三个化合物的吸收性和预测其吸收机制,对它们的双向透过性进行了研究,并计算了相应的表观渗透系数(Papp)。在三个受试化合物中,原人参三醇差向异构体化合物1和2显示了良好的吸收性,Papp值在1×10–5 cm/s数量级;而化合物3判断为吸收不良的化合物,其Papp值小于1×10–7 cm/s。三个化合物由于结构上的差异,在细胞内产生了不同程度的蓄积。维拉帕米抑制P糖蛋白的转运实验结果表明,化合物1和2在MDCK-p Ha MDR细胞单层模型中的转运机制不仅仅是单纯的被动扩散。本文的研究结果为化合物1和2作用于脑的研究提供了实验依据。

关 键 词：20（S）-Protopanaxatriol 20（R）-Protopanaxatriol Dammar-20（22）E 24-diene-3β 6α 12β-triol MDCK-pHaMDR Permeability Blood-brain barrier 

分 类 号：R285[医药卫生—中药学]