坤复康片中芍药内酯苷在Caco-2细胞模型中的吸收特征研究

Characterization of the Intestinal Absorption of Albiflorin from Kunfukang Tablets in Caco-2 Cell Monolayer Model

关键词:  芍药内酯苷  Caco-2  口服给药  吸收机制

Key words:  albiflorin  Caco-2  oral administration  absorption mechanism

摘要:

目的 研究坤复康片中的芍药内酯苷在Caco-2细胞模型中的跨膜吸收特征，探讨人小肠对芍药内酯苷的吸收和转运。方法 研究了不同药物浓度、pH值、温度和抑制剂对芍药内酯苷在Transwell细胞培养板中从顶膜(apical，AP)到基底(basolateral，BL)的双向渗透吸收的影响。结果 芍药内酯苷以3种测试浓度给药时(5，20和100 μmol·L^-1)，从AP到BL方向的表观渗透系数(P_app)值范围为(3.27~5.37)×10^-7 cm·s^-1。相反，从BL到AP，P_app值范围为(6.64~9.63)×10^-7 cm·s^-1。数据表明，芍药内酯苷转运具有pH和温度依赖性。芍药内酯苷的细胞通透性受多种抑制剂影响，包含Na⁺/K⁺离子通道抑制剂钒酸钠，多耐药蛋白抑制剂MK571和吲哚美辛及乳腺癌耐药蛋白抑制剂芹菜素。当坤复康溶液加入后，芍药内酯苷从AP到BL方向的P_app值显著增加。结论 芍药内酯苷在Caco-2细胞模型中的肠道吸收较差，其吸收机制可能涉及多种蛋白介导的主动转运。

Abstract:

OBJECTIVE To study the transmembrane absorption characteristics of paeoniflorin from Kunfukang tablets in Caco-2 cell model, and to explore the absorption and transport of paeoniflorin in human small intestine.METHODS The effects of different drug concentrations, pH, temperature and inhibitors on the bidirectional permeability of albiflorin from the apical(AP) to the basolateral(BL) side of Transwell plate cells and in the reverse direction was studied.RESULTS When administered at three concentrations(5, 20 and 100 μmol·L^-1), the apparent permeability coefficient(P_app) value in the AP-to-BL direction ranged in (3.27-5.37)×10^-7 cm·s^-1. In the reverse direction, BL-to-AP, the P_app value was ranged in (6.64-9.63)×10^-7 cm·s^-1. The data indicated that albiflorin transport was pH-and temperature-dependent. The permeability of albiflorin was affected by treatment with various inhibitors, such as Na⁺/K⁺ pump inhibitors sodium vanadate, multidrug resistance protein inhibitors MK571 and indomethacin, as well as the breast cancer resistance protein inhibitor apigenin. After the addition of Kunfukang pills, the P_app values in the AP-to-BL direction increased significantly.CONCLUSION Albiflorin is shown to be a poorly absorbed compound in the Caco-2 cell monolayer model, and its absorption mechanism may involve a variety of protein mediated active transport.