Abstract

1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent to which main components are absorbed and the mechanisms involved are controversial.

2. In this study, MDCK cell model was used to determine the permeability characteristics and interaction between the major components of Si-Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid.

3. The transport of the major components was concentration-dependent in both directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic acid was significantly reduced at 4 °C or in the presence of NaN3. Additionally, the efflux of paeoniflorin and naringin were apparently reduced in the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved in the transport of glycyrrhizic acid. However, the results indicated that saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the combined incubation of four major components had a powerful sorbefacient effect than a single drug used alone which may be regulated by tight junctions.

4. Taken together, our study provides useful information for pharmacological applications of Si-Ni-San and offers new insights into this ancient decoction for further researches, especially in drug synergism.

抽象的

1. Si-Ni-San（SNS）具有广泛的治疗作用，但是，主要成分的吸收程度和涉及的机制仍存在争议。

2.在本研究中，使用MDCK细胞模型确定了硅镍皂苷a，pa药苷，柚皮苷和甘草酸的主要成分之间的渗透性特征和相互作用。

3.主要成分的运输在两个方向上均与浓度有关。此外，在4°C或存在NaN3的情况下，pa药苷，柚皮苷和甘草酸的转运明显减少。另外，在P-gp抑制剂维拉帕米存在下，pa药苷和柚皮苷的外排明显减少。甘草酸的转运明显受到MRP2抑制剂的抑制，表明MRP2可能参与了甘草酸的转运。但是，结果表明皂苷a主要被被动扩散吸收。此外，四种主要成分的组合孵育比单独使用的单一药物具有更强的吸附作用，后者可能受到紧密连接的调节。

4.总的来说，我们的研究为Si-Ni-San的药理应用提供了有用的信息，并提供了对该古老汤剂的新见解，以供进一步研究，特别是在药物协同作用方面。