Duan Jingze, Xie Yan, Luo Huilin, Li Guowen, Wu Tao, Zhang Tong
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Food Chem Toxicol. 2014 Apr;66:313-20. doi: 10.1016/j.fct.2014.02.003. Epub 2014 Feb 10.
Flavonoid isorhamnetin occurs in various plants and herbs, and demonstrates various biological effects in humans. This work will clarify the isorhamnetin absorption mechanism using the Caco-2 monolayer cell model. The isorhamnetin transport characteristics at different concentrations, pHs, temperatures, tight junctions and potential transporters were systemically investigated. Isorhamnetin was poorly absorbed by both passive diffusion and active transport mechanisms. Both trans- and paracellular pathways were involved during isorhamnetin transport. Active transport under an ATP-dependent transport mechanism was mediated by the organic anion transporting peptide (OATP); isorhamnetin's permeability from the apical to the basolateral side significantly decreased after estrone-3-sulfate was added (p<0.01). Efflux transporters, P-glycoproteins (P-gp), breast cancer resistance proteins (BCRP) and multidrug resistance proteins (MRPs) participated in the isorhamnetin transport process. Among them, the MRPs (especially MRP2) were the main efflux transporters for isorhamnetin; transport from the apical to the basolateral side increased 10.8-fold after adding an MRP inhibitor (MK571). This study details isorhamnetin's cellular transport and elaborates isorhamnetin's absorption mechanisms to provide a foundation for further studies.
黄酮类化合物异鼠李素存在于多种植物和草药中，并在人体中表现出多种生物学效应。这项工作将使用Caco-2单层细胞模型阐明异鼠李素的吸收机制。系统研究了不同浓度、pH值、温度、紧密连接和潜在转运体条件下异鼠李素的转运特性。异鼠李素通过被动扩散和主动转运机制的吸收都很差。异鼠李素转运过程涉及跨细胞和细胞旁途径。ATP依赖的主动转运机制由有机阴离子转运肽（OATP）介导；添加硫酸雌酮3-酯后，异鼠李素从顶端到基底外侧的渗透率显著降低（p<0.01）。外排转运体、P-糖蛋白（P-gp）、乳腺癌耐药蛋白（BCRP）和多药耐药蛋白（MRP）参与了异鼠李素的转运过程。其中，MRP（尤其是MRP2）是异鼠李素的主要外排转运体；添加MRP抑制剂（MK571）后，从顶端到基底外侧的转运增加了10.8倍。本研究详细阐述了异鼠李素的细胞转运过程，并阐明了异鼠李素的吸收机制，为进一步研究提供了基础。
