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Abstract
1. Although emerging evidence indicates the therapeutic effects of Zhizi Bopi Decoction, the extent to which essential ingredients are absorbed and the possible synergistic actions are poorly understood.
2. In this study, MDCK cell model was used to determine the bi-directional permeability and interaction between the main components (geniposide, berberine and glycyrrhizic acid) of Zhizi Bopi Decoction.
3. The transport of the active ingredients was concentration-dependent in both directions. Moreover, the Papp (AP-BL) values of berberine and glycyrrhizic acid were significantly reduced when co-incubation with an ATP inhibitor. Additionally, uptake of berberine, glycyrrhizic acid were clearly inhibited by the inhibitors of P-glycoprotein and MRP2, indicating that P-gp and MRP2 may be involved in the transport of berberine and glycyrrhizic acid, respectively. However, it was found that geniposide may be purely passive diffusion. Furthermore, the combined incubation of geniposide with berberine and glycyrrhizic acid had a powerful sorbefacient effect than use of a single drug alone which may be regulated by tight junctions.
4. In summary, our study provides useful information for pharmacological applications of Zhizi Bopi Decoction and offers new insights into this ancient decoction for further researches, especially in drug synergism.
Acknowledgements
The authors thank Pro. Biwei Song for offering MDCK cell line.
Declaration of interest
This project was supported by the National Science Foundation of China (nos:81273526, and 81473268), Anhui provincial key Scientific and technological project (1301042212), Anhui Provincial Natural Science Foundation (1308085MH145), Specialized Research Fund for the Doctoral Program of Higher Education (20123420120001).
Supplemetary material available online