In Vitro and In Situ Characterization of the Intestinal Absorption of Capilliposide B and Capilliposide C from Lysimachia capillipes Hemsl
In Vitro and In Situ Characterization of the Intestinal Absorption of Capilliposide B and Capilliposide C from Lysimachia capillipes Hemsl
复制标题
珍珠菜中毛脂苷 B 和毛脂苷 C 肠道吸收的体外和原位表征
DOI：
10.3390/molecules24071227
复制
发表时间：
2019-03
期刊：
影响因子：
4.6
通讯作者：
Gu Mancang
中科院分区：
文献类型：
--
作者：
Zhang Xu;Cheng Xiao;Wu Yali;Feng Di;Qian Yifan;Chen Liping;Yang Bo;Gu Mancang
本研究的目的是确定中草药金钱草中的毛细管苷B(CAPB)和毛细管苷C(CAPC)的肠道吸收过程和机制。用LC-MS分析不同肠段的药物浓度、时间和行为等基本参数。采用Caco-2细胞单层和单次肠道灌流(SPIP)模型，检测CAPB和CAPC对P-糖蛋白(P-gp)抑制剂(异搏定)、多药耐药相关蛋白2(MRP2)抑制剂(吲哚美辛)、细胞色素P450蛋白3A4(CYP3A4)抑制剂(酮康唑)以及P-gp、MRP2和CYP3A4(环孢素A)联合抑制剂的敏感性。因此，CAPB和CAPC在肠道中的吸收都很差，并表现出节段性的通透性。维拉帕米、消炎痛联合应用可显著提高CAPB和CAPC的肠通透性。此外，酮康唑和环孢菌素A也能提高CAPB的肠道通透性。结论：CAPB和CAPC的肠道吸收机制涉及促进被动扩散、外排转运和酶介导的代谢等过程。CAPB和CAPC均可作为P-gp和MRP2的底物。然而，CAPB可能与CYP3A4系统相互作用。
The goal of this investigation was to determine the processes and mechanism of intestinal absorption for capilliposide B (CAPB) and capilliposide C (CAPC) from the Chinese herb, Lysimachia capillipes Hemsl. An analysis of basic parameters, such as drug concentrations, time, and behavior in different intestinal segments was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The susceptibility of CAPB and CAPC to various inhibitors such as P-glycoprotein (P-gp) inhibitor (verapamil); multidrug resistance-associated protein 2 (MRP2) inhibitor (indomethacin); cytochrome P450 protein 3A4 (CYP3A4) inhibitor (ketoconazole); and the co-inhibitor of P-gp, MRP2 and CYP3A4 (cyclosporine A) were assessed using both caco-2 cell monolayer and single-pass intestinal perfusion (SPIP) models. As a result, CAPB and CAPC are both poorly absorbed in the intestines and exhibited segment-dependent permeability. The intestinal permeability of CAPB and CAPC were significantly increased by the co-treatment of verapamil, indomethacin. In addition, the intestinal permeability of CAPB was also enhanced by ketoconazole and cyclosporine A. It can be concluded that the intestinal absorption mechanisms of CAPB and CAPC involve processes such as facilitated passive diffusion, efflux transporters, and enzyme-mediated metabolism. Both CAPB and CAPC are suggested to be substrates of P-gp and MRP2. However, CAPB may interact with the CYP3A4 system.
登录
查看更多内容
通过 LC→QTRAP→MS/MS 测定 Capilliposide B 和 Capilliposide C 的代谢稳定性和代谢物表征
影响因子：
5.4
作者：
Cheng Z;Zhou X;Du Z;Li W;Hu B;Tian J;Zhang L;Huang J;Jiang H
通讯作者：
Jiang H
DOI：
10.12659/msm.901183
发表时间：
2017-05-02
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Shen Z;Xu L;Li J;Zhang N
通讯作者：
Zhang N
影响因子：
1.7
作者：
Lei Xin;Xiao-hui Liu;Jun Yang;Hongyi Shen;G. Ji;Xiufeng Shi;Yan Xie
通讯作者：
Lei Xin;Xiao-hui Liu;Jun Yang;Hongyi Shen;G. Ji;Xiufeng Shi;Yan Xie
影响因子：
3.9
作者：
S. Vaessen;M. V. van Lipzig;R. Pieters;C. Krul;H. Wortelboer;E. van de Steeg
通讯作者：
S. Vaessen;M. V. van Lipzig;R. Pieters;C. Krul;H. Wortelboer;E. van de Steeg
影响因子：
2.2
作者：
Huadong Sun;K. Pang
通讯作者：
Huadong Sun;K. Pang