Effects of glingolide and flavone on amyloid β-protein transcytosis across the blood -brain barrier in hypoxic condition

ZHANG Yun-sha; YANG Lin; PANG Geng; LI Hu-hu; FAN Ying-chang; JIANG Xi-juan

Abstract：Objective To observe the effects of glingolide and ginkgo flavone on β-amlyoid (Aβ) transcytosis across the blood -brain barrier (BBB) in hypoxic condition and its correlation with BBB transporter RAGE and LRP1. Methods The BBB models were established by co -culturing rat brain microvascular endothelial cells and astrocytes in vitro in the Transwell device, and divided into control group, hypoxic group, Glingolide or Ginkgo Flavone alone and com-bined treatment groups.The basolateral -to -apical permeability of Aβwas detected by using enzyme -linked immu-nosorbent assay (ELISA).The BBB integrity was evaluated by measuring transepithelial -astocyte electrical resistance (TEER) and FD4 permeability rate.The expression of RAGE and LRP1 was assessed by RT -qPCR and Western blot. Results The efflux rate of Aβacross the BBB under hypoxic condition was lower compared with that in the control group. The efflux rate of Aβwas significantly increased after application of glingolide and/or ginkgo flavone.The BBB integrity was not damaged with any treatments.RAGE expression was up -regulated while LRP1 expression was down -regulated under hypoxic condition.Administration of any single compound enhanced the inhibitory effect of low oxygen on LRP1 without affecting RAGE.The RAGE was down -regulated but LRP1 was up -regulated in combined treatment.Conclu-sion Glingolide and ginkgo flavone can promote Aβefflux through intervening RAGE and LRP1 expression to delay the development of Alzheimer′s disease.