Bilobalide reversibly modulates blood-brain barrier permeability through promoting adenosine A1 receptor-mediated phosphorylation of actin-binding proteins.
Biochem Biophys Res Commun
; 526(4): 1077-1084, 2020 06 11.
Article
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| MEDLINE
| ID: mdl-32312522
ABSTRACT
Bilobalide, one of the key bioactive components of Ginkgo biloba leaves, exerts prominent neuroprotective properties in central nervous system (CNS) disease. However, the effect of bilobalide on blood-brain barrier (BBB) permeability remains unknown. In this study, we investigated the effect of bilobalide on BBB permeability and its potential mechanism involved. Both the in vitro and in vivo results showed that significant enhancement of BBB permeability was found following bilobalide treatment, evidenced by the reduced transendothelial electrical resistance (TEER), the increased fluorescein sodium (Na-F) penetration rate in vitro and the leakage of FITC-dextran in vivo. Transmission electron microscope (TEM) images demonstrated that bilobalide modulated BBB permeability by changing the ultrastructure of tight junctions (TJs). In addition, actin-binding proteins ezrin, radixin and moesin (ERM) and Myosin light chain (MLC) phosphorylation was observed following bilobalide treatment. Moreover, the effect of bilobalide on TEER reduction and ERM/MLC phosphorylation was counteracted by adenosine A1 receptor (A1R) siRNA. The current findings suggested that bilobalide might reversibly modulate BBB permeability by the alteration of TJs ultrastructure through A1R-mediated phosphorylation of actin-binding proteins.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Barrera Hematoencefálica
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Receptor de Adenosina A1
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Bilobálidos
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Proteínas de Microfilamentos
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2020
Tipo del documento:
Article