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.

中文翻译：

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araloside A原位单次肠道灌注和体外Caco-2细胞模型的肠道吸收机制。

Araloside A是一种三萜皂苷，具有广泛的药理活性，如刺激纤维蛋白溶解，预防凝血，抑制肾素和降低血压。我们以前的报告发现该化合物具有很差的绝对生物利用度。但是，尚未在小肠或Caco-2细胞模型中研究其吸收的潜在机制。在这项研究中，在Caco-2细胞单层和Sprague-Dawley大鼠的原位肠单次灌流模型中研究了araloside A的吸收机制。分析了诸如化合物浓度，时间，温度，细胞旁通路，不同肠段等基本参数的影响，以及对araloside A吸收过程对各种抑制剂治疗的敏感性，评估了P-gp抑制剂维拉帕米，多药抗性蛋白2抑制剂（MRP2）MK571和吲哚美辛，乳腺癌抗性蛋白（BCRP）抑制剂Ko143和利血平以及内吞抑制剂氯丙嗪。可以发现，araloside A的肠道吸收机制可能涉及多种转运途径，例如被动扩散，旁细胞途径以及外排转运蛋白的参与。