In vitro characterization of ABC transporters involved in the absorption and distribution of liensinine and its analogs
In vitro characterization of ABC transporters involved in the absorption and distribution of liensinine and its analogs
复制标题
参与莲西宁及其类似物吸收和分布的 ABC 转运蛋白的体外表征
DOI：
10.1016/j.jep.2013.08.061
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发表时间：
2013-11-25
影响因子：
5.4
通讯作者：
Zeng, Su
中科院分区：
文献类型：
--
作者：
Yu, Lushan;Shen, Qi;Zeng, Su
民族药理学相关性：莲子心，干燥的嫩子叶和莲子根。（Fam。睡莲科睡莲属睡莲科睡莲心碱及其类似物甲基莲心碱和异莲心碱是莲子心的主要活性成分。本研究的目的是探讨莲心碱、甲基莲心碱和。材料和方法：以Caco-2、MDCK、MDCK-MDR 1和MDCK-MRP 2为模型，研究异莲心碱的跨细胞转运和蓄积。在MDCK-MDR 1细胞中进一步进行细胞蓄积和转运实验。GF 120918和环孢素A被发现完全抑制外排，这些生物碱的净外排率在浓度范围内表现出饱和。结论：莲心碱、甲基莲心碱和异莲心碱均为P-gp的底物，而MRP 2不参与莲心碱的转运过程，提示P-gp可能参与了莲心碱、甲基莲心碱和异莲心碱在MDCK和MDCK-MRP 2细胞中的吸收和分布。(C)2013爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Lotus plumule, the dried young cotyledon and radicle of the Nelumbo nucifera Gaertn. (Fam. Nymphaeaceae) ripe seed, is a famous Traditional Chinese Medicine to remove heat from the heart, anchor the mind, improve seminal emission, and arrest bleeding for centuries in China. Liensinine and its analogs neferine and isoliensinine are the major active components in lotus plumule. Aim of the study is to investigate the association of liensinine, neferine, and. isoliensinine with efflux transporters.Materials and methods: Caco-2, MDCK, MDCK-MDR1, and MDCK-MRP2 were used as cell models for the transcellular transport and accumulation studies.Results: The results obtained in Caco-2 cells suggested that P-glycoprotein (P-gp) might be involved in transcellular transport. Cellular accumulation and transport experiments were further performed in MDCK-MDR1 cells. GF120918 and cyclosporine A were found to completely inhibit the efflux, and the net efflux ratios of these alkaloids exhibited saturation over the concentration range. No significant differences in liensinine accumulation and transport were observed between MDCK and MDCK-MRP2 cells.Conclusions: These results demonstrated that liensinine, neferine, and isoliensinine are substrates of P-gp, whereas MRP2 is not involved in the transport process, suggesting that P-gp might be responsible for the absorption and distribution of the 3 alkaloids. (C) 2013 Elsevier Ireland Ltd. All rights reserved.