Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model

International Journal of Molecular Sciences

Xiang Fan¹  Lijuan Chai¹  Han Zhang¹  Yuefei Wang¹  Boli Zhang¹  Xiumei Gao¹ 

[1] Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China;

关键词: borneol;    P-glycoprotein;    brain microvascular endothelial cells;    NF-κB;    blood brain barrier;   

DOI  :  10.3390/ijms161126051

来源: mdpi

【 摘 要 】

P-glycoprotein (P-gp) on brain microvascular endothelial cells (BMECs) that form the blood brain barrier (BBB), influences transportation of substances between blood and brain. The objective of this study was to characterize the effects of borneol on P-gp efflux function on BBB and explore the potential mechanisms. We established an in vitro BBB model comprised of rat BMECs and astrocytes to measure the effects of borneol on the known P-gp substrates transport across BBB, and examined the function and expression of P-gp in BMECs and the signaling pathways regulating P-gp expression. Borneol increased intracellular accumulation of Rhodamine 123, enhanced verapamil and digoxin across the BBB in vitro model, and depressed mdr1a mRNA and P-gp expression. Borneol could activate nuclear factor-κB (NF-κB) and inhibition of NF-κB with MG132 (carbobenzoxy-Leu-Leu-leucinal) and SN50 (an inhibitory peptide) obscuring the P-gp decreases induced by borneol. These data suggested that borneol depresses P-gp function in BMECs by a NF-κB signaling medicated mechanism in a BBB in vitro model.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.