期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 526, 期 4, 页码 1077-1084出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.03.186
关键词
Bilobalide; Blood-brain barrier; Adenosine receptor; Cytoskeleton protein; Central nervous system
资金
- Nature Science Foundation of China (NSFC) [81473588]
- Guangdong Science and Technology Department [2013A022100041, 2016B050501003, 2017B050504005]
- Traditional Chinese Medicine Bureau of Guangdong Province, China [20191203]
- Natural Science Foundation of Guangdong Province [2018A030313391]
- Medical Science and Technology Research Fund of Guangdong Province [A2019531]
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. (C) 2020 Elsevier Inc. All rights reserved.
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