Effect Of Beta-elemene On Transport Of Geiftinib Acrossblood-brain Barrier In Vitro

Aim: To develop a simple model of blood-brain barrier (BBB) permeation in vitro,and to investigate whether beta-elemene affect the transport of gefitinib across BBB byinhibiting P-glycoprotein (P-GP) activity.Methods: Co-culture of primary-cultured, rat brain microvascular endothelial cells(rBMECs) and astrocytes was established in a transwell device to mimic in vivo BBB.LC/MS/MS method was applied to assay transendothelial transport amount of gefitiniband calculate the apparent permeability coefficient (Papp).Rhodamine-123across BBB invitro was measured to examine the function of P-GP.Results: The endothelial permeability coefficient (Pe) of sodium fluorescein (FLU) was4.90±1.31×10-6cms-1, associated with the transendothelial electrical resistance (TEER)of317.56±19.34Ωcm2, indicating the integrity of rBMECs monolayer barrier. Inpresence of beta-elemene (30μg/ml), the transport amount of gefitinib (1μg/ml) acrossrBMECs monolayer was increased by2.30-fold. Mechanically, beta-elemene couldinhibit the efflux transport of P-GP and increase the transport amount of rho123acrossBBB, suggesting that the interaction of gefitinib and beta-elemene was mediated byP-GP.Conclusion: Beta-elemene could promote the transport of gefitinib across in vitroBBB by inhibiting P-GP activity.