期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 17, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms17091418
关键词
ruscogenin; ischemic stroke; blood-brain barrier; inflammasome; MAPK
资金
- National Natural Science Foundation of China [81274004]
- Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education through Priority Academic Program Development of Jiangsu Higher Education Institutions
- Program for Graduate Innovation of Jiangsu Province [KYLX_0608]
- Jiangsu Province Plan for Collaborative Innovation, Project Program of the State Key Laboratory of Natural Medicines of China Pharmaceutical University [JKGZ201107]
Ruscogenin, an important steroid sapogenin derived from Ophiopogon japonicus, has been shown to inhibit cerebral ischemic injury. However, its potential molecular action on blood-brain barrier (BBB) dysfunction after stroke remains unclear. This study aimed to investigate the effects of ruscogenin on BBB dysfunction and the underlying mechanisms in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice and oxygen-glucose deprivation/reoxygenation (OGD/R)-injured mouse brain microvascular endothelial cells (bEnd.3). The results demonstrated that administration of ruscogenin (10 mg/kg) decreased the brain infarction and edema, improved neurological deficits, increased cerebral brain flow (CBF), ameliorated histopathological damage, reduced evans blue (EB) leakage and upregulated the expression of tight junctions (TJs) in MCAO/R-injured mice. Meanwhile, ruscogenin (0.1-10 mu M) treatment increased cell viability and trans-endothelial electrical resistance (TEER) value, decreased sodium fluorescein leakage, and modulated the TJs expression in OGD/R-induced bEnd.3 cells. Moreover, ruscogenin also inhibited the expression of interleukin-1 (IL-1) and caspase-1, and markedly suppressed the expression of Nucleotide-binding domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) and thiredoxin-interactive protein (TXNIP) in vivo and in vitro. Furthermore, ruscogenin decreased reactive oxygen species (ROS) generation and inhibited the mitogen-activated protein kinase (MAPK) pathway in OGD/R-induced bEnd.3 cells. Our findings provide some new insights into its potential application for the prevention and treatment of ischemic stroke.
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