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Ginsenoside Rb1 (Rb1) has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb1 transport at the blood--brain barrier (BBB) using primary cultured rat brain microvascular endothelial cells (rBMEC), an in vitro BBB model. The initial uptake velocity of Rb1 in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor. Furthermore, the transport of Rb1 into rBMEC was significantly diminished in the presence of natural substrate a-D-glucose, suggesting a facilitated transport of Rb1 via GLUT1 transporter. The impact of GLUT1 on the distribution of Rb1 between brain and plasma was studied experimentally in rats. Administration of phloretin (5 mg/kg, i.v.) to normal rats for consecutive 1 week before Rb1 (10 mg/kg, i.v.) at 0.5, 2, and 6 h did not alter Rb1 concentrations in plasma, but resulted in significant decreased brain concentrations of Rb1 compared to in the phloretin-untreated normal rats (489.6 ± 58.3 versus 105.1 ± 15.1 ng/g, 193.8 ± 11.1 versus 84.8 ±4.1 ng/g, and 114.2 ± 24.0 versus 39.9 ±4.9 ng/g, respectively). The expression of GLUT1 in the phloretin-treated group by western blotting analysis in vitro and in vivo experiments was significantly decreased, indicating that the decreased transport of Rb1 in brain was well related to the down-regulated function and level of GLUT1. Therefore, our in vitro and in vivo results indicate that the transport of Rb1 at the BBB is at least partly mediated by GLUT1 transporter. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb 1 (Rb 1 ) has been demonstrated its protection for central nervous system and is apparently highly distributed to the brain. The objective of this study was to characterize Rb 1 transport at the blood-brain barrier (BBB) using primary cultured rat brain microvascular endothelial cells (rBMEC), an in vitro BBB model. The initial uptake velocity of Rb 1 in rBMEC was temperature- and concentration-dependent, and was significantly reduced by phloretin, an inhibitor of GLUT1 transporter, but was independent of metabolic inhibitor. Furthermore, the transport of Rb 1 into rBMEC was significantly diminished in the presence of natural substrate α-D-glucose, suggesting a facilitated transport of Rb 1 via GLUT1 transporter. The impact of GLUT1 on the distribution of Rb 1 between brain and plasma was studied experimentally in rats. Administration of phloretin (5 mg/kg, i.v.) to normal rats for consecutive 1 week before Rb 1 (10 mg/kg, i.v.) at 0.5, 2, and 6 h did not alter Rb 1 concentrations in plasma, but resulted in significant decreased brain concentrations of Rb 1 compared to in the phloretin-untreated normal rats (489.6 ± 58.3 versus 105.1 ± 15.1 ng/g, 193.8 ± 11.1 versus 84.8 ± 4.1 ng/g, and 114.2 ± 24.0 versus 39.9 ± 4.9 ng/g, respectively). The expression of GLUT1 in the phloretin-treated group by western blotting analysis in vitro and in vivo experiments was significantly decreased, indicating that the decreased transport of Rb 1 in brain was well related to the down-regulated function and level of GLUT1. Therefore, our in vitro and in vivo results indicate that the transport of Rb 1 at the BBB is at least partly mediated by GLUT1 transporter.