title: Uptake characteristics of pinocembrin and its effect on p-glycoprotein at the blood-brain barrier in in vitro cell experiments.
abstract: One purpose of the present study was to investigate the uptake characteristics of pinocembrin (PCB) and its effect on p-glycoprotein (P-gp) at the blood-brain barrier (BBB). Cultured rat brain microvascular endothelial cells (rBMECs) were used as an in vitro BBB model. Experiments were conducted to examine time-, concentration-, and temperature-dependent elements of PCB uptake, and the effect of classical P-gp inhibitors, cyclosporin A (CsA) and verapamil (Ver), on the steady-state uptake of PCB. Uptake of rhodamine 123 (Rho123), the typical P-gp substance, was measured with or without PCB. Meanwhile, the protein level of P-gp after incubation with PCB was detected by Western blot assay. The results demonstrated that PCB uptake by rBMECs was in a time- and concentration-dependent manner. CsA and Ver slightly increased PCB steady-state uptake by less than 10% (p>0.05). Similar results were observed in Rho123 uptake by co-administration of PCB. Further results were obtained by Western blot assay. PCB might not affect P-gp expression in rBMECs. Overall, the findings demonstrate that the passive transport process may be the main process for PCB to pass through the BBB, and P-gp is likely to have a little effect on the PCB transport process. Furthermore, PCB may not affect the functional activity and the protein expression of the P-gp transporter at the BBB.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Yang
authors.forename: Xiao
authors.initials: X
authors.lastname: Sun
authors.forename: Yun
authors.initials: Y
authors.lastname: Qi
authors.forename: Chao
authors.initials: C
authors.lastname: Mei
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Sun
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D020112:Rhodamine 123 / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044950:Flavanones; D018696:Neuroprotective Agents; D020112:Rhodamine 123; D016572:Cyclosporine; C016063:pinocembrin; D014700:Verapamil