Program

PO2-12-6

Ligustilide ameliorates the permeability of the blood-brain barrier model in vitro during oxygen-glucose deprivation injury

[Speaker] Ning Wang:1,2,3
[Co-author] Jing Li:1, Guangyun Wang:1
1:School of Pharmacy, Anhui University of Chinese Medicine, China, Anhui University of Chinese Medicine, China, 2:Key Laboratory of Xinan Medicine, Ministry of Education, Hefei, China, 3:Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei, China

Chuanxiong rhizome has been widely used for the treatment of cerebral vascular disease in traditional Chinese medicine. The integrity of BBB closely is linked to cerebral vascular disease. Although the cerebal vascular protective effects of ligustilide, the major bioactive component in Chuanxiong rhizome, had been reported previously, its effects on the blood-brain barrier (BBB) has not been fully explored. In this study, the effects of ligustilide on BBB permeability and the underlying molecular mechanisms have been investigated using the model of BBB established by co-culturing brain microvascular endothelial cells (BMECs) and astroglial cells (AC) isolated from the rat brain. The damaged model of BBB has been simulated with oxygen and glucose deprivation (OGD) to induce ischemia. BBB permeability was assessed by transendothelial electrical resistance (TEER) values, the permeance of fluorescein and high performance liquid chromatography . Changes in protein expression of HIF-1a, vascular endothelial growth factor (VEGF), occludin, ZO-1 and aquaporin-4 (AQP-4) had been determined by Western blotting. Our results indicated that OGD significantly increased the permeability in the co-culture BBB model. This OGD-induced increase in permeability could suppressed by ligustilide in a concentration dependent manner. Also, ligustilide promoted both gene and protein expression of tight junction (TJ) proteins (Occludin and ZO-1). Ligustilide suppressed the upregulation of HIF-1a, VEGF, AQP-4 in the BBB model induced by OGD. In conclusion, ligustilide is capable to restore the OGD-impaired BBB function in an in vitro BBB model, which is associated with increasing the expression of TJ proteins and decreasing the expression of HIF-1a, VEGF and AQP-4.
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