论文部分内容阅读
Objective Genistein is a good candidate as an alternative to estrogen replacement therapy for Aizheimer disease (AD)because of the effects in ameliorating learning or memory deficits of AD without increased risk of certain types of hormone-sensitive tumors.The present study aims to investigate the possibility of P-gp as a potential target for genistein to prevent AD.Methods Primary rat brain microvascular endothelial cells (rBMEC) were cultured in vitro and used to establish the BBB model.The unidirectional transport of Aβ-42 from basolateral side to apical side across rBMEC monolayers was determined to evaluate the effect of genistein on Aβ clearance.The functional alterations of P-gp induced by genistein were evaluated by rhodamine 123 accumulation and digoxin bidirectional transport.Examine the effects of genistcin on the expression of Mdr 1 a/Mdr lb gene by Real-Time PCR and P-gp by Western Blot.Results Papp(BL-AP) values of Aβ42 across the BBB model were concentration-dependently increased by 5 μM or higher concentration of genistein in both physiological and pathological BBB model.Genistein decreased cellular retention of rhodamine 123 and increased the efflux radio of digoxin in a concentration dependent manner.Genistein could concentrationdependently up-regulate Mdrla and Mdrlb expression for short-term, but for long-term effect, only 10 μM genistein increased the expression of Mdrlb.P-gp expression was also up-regulated by genistein in short-term and long-term.Conclusion Genistein can enhance Aβ-42 clearance across BBB in both physiological and pathological state, and the underlying mechanism may be associated with reinforced P-gp functional activity and increasing the expression levels of P-gp.