Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
School of Basic Medical Science, Shaanxi University of Chinese Medicine, Xianyang 712046, China.
Biomed Pharmacother. 2018 Oct;106:1563-1569. doi: 10.1016/j.biopha.2018.07.117. Epub 2018 Jul 27.
Araloside A is a triterpenoid saponin,which exhibits a broad spectrum of pharmacological activities, such as stimulating fibrinolysis, preventing coagulant, inhibiting renin, and decreasing blood pressure. Our previous report found that the compound exhibits a poor absolute bioavailability. However the underlying mechanisms of its absorption have not been investigated in the small intestine or in a Caco-2 cell model. In this study, the absorption mechanisms of araloside A were investigated in a Caco-2 cell monolayer and in a single-pass intestinal perfusion in situ model with Sprague-Dawley rats. The effects of basic parameters, such as compound concentration, time, temperature, paracellular pathway, different intestinal segments were analyzed, and the susceptibility of araloside A absorption process to treatment with various inhibitors, such as the P-gp inhibitor verapamil, the multidrug resistance protein2 inhibitors (MRP2) MK571 and indomethacin, the breast cancer resistance protein (BCRP) inhibitors Ko143 and reserpine, and endocytosis inhibitor chlorpromazine were assessed. It can be found that the mechanisms of intestinal absorption of araloside A may involve multiple transport pathways, such as passive diffusion, the paracellular pathway, as well as the participation of efflux transporters.
阿拉皂苷 A 是一种三萜皂苷，具有广泛的药理活性，如促进纤溶、抗凝、抑制肾素、降低血压。我们之前的报告发现，该化合物的绝对生物利用度较差。然而，其在小肠或 Caco-2 细胞模型中的吸收机制尚未得到研究。在这项研究中，阿拉皂苷 A 的吸收机制在 Caco-2 细胞单层和单次通过肠灌注原位模型中进行了研究，使用 Sprague-Dawley 大鼠。分析了化合物浓度、时间、温度、细胞旁途径等基本参数的影响，以及阿拉皂苷 A 吸收过程对各种抑制剂（如 P-糖蛋白抑制剂维拉帕米、多药耐药蛋白 2 抑制剂（MRP2）MK571 和吲哚美辛、乳腺癌耐药蛋白（BCRP）抑制剂 Ko143 和利血平）和内吞抑制剂氯丙嗪处理的敏感性。可以发现，阿拉皂苷 A 的肠吸收机制可能涉及多种转运途径，如被动扩散、细胞旁途径以及外排转运体的参与。
