Hepatic Uptake Mechanism of Ophiopogonin D Mediated by Organic Anion Transporting Polypeptides.

BACKGROUND AND OBJECTIVES

Ophiopogonin D (OPD) is one of the main active ingredients of SMI (Shenmai injection) which is widely used in clinical practice in China. Our previous study indicated  that OPD might be transported from blood into liver mediated by organic anion transporting polypeptides (OATPs/oatps). This study aims to explore the hepatic uptake mechanism of OPD in rat and human.

METHODS

Rosuvastatin (a competitive inhibitor of oatp1b2, oatp1a1, and oatp1a4), glycyrrhizic acid (a specific inhibitor of oatp1b2), digoxin (a specific inhibitor of oatp1a4), bromosulfophthalein (BSP), and ibuprofen (a specific inhibitor of oatp1a1) were used to study the uptake of OPD in rat hepatocytes. Furthermore, the uptake of OPD in human OATP1B1*1a-HEK293T cells was also investigated, and rosuvastatin, BSP, rifampin, and glycyrrhizic acid were all used as the competitive inhibitor of OATP1B1.

RESULTS

OPD can be taken in rat primary hepatocytes with K (Michaelis Menten constant) of 8.10 μM and V (maximum velocity) of 54.39 nmol/min/mg protein. The uptake of OPD in rat hepatocytes was inhibited significantly by rosuvastatin and glycyrrhizic acid. However, digoxin, BSP, and ibuprofen had no effect on the uptake of OPD in rat hepatocytes. OPD can also be transported by OATP1B11a-HEK293T cells with K of 5.50 μΜ and V of 29.07 nmol/min/mg protein. Compared with rosuvastatin, OPD has a higher affinity with OATP1B1 and can be transported faster in unit time. Rosuvastatin, BSP, rifampin, and glycyrrhizic acid all exhibited a certain extent inhibitory effect on the transport of OPD in OATP1B11a-HEK293T cells.

CONCLUSIONS

Overall, this study indicates OATP1B1 in human and oatp1b2 in rats might participate in the hepatic uptake of OPD.