Brain Transport Profiles of Ginsenoside Rb1 by Glucose Transporter 1: In Vitro and in Vivo

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 alpha-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.