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Ligustilide Ameliorates the Permeability of the Blood–Brain Barrier Model In Vitro During Oxygen–Glucose Deprivation Injury Through HIF/VEGF Pathway

Wu, Sipeng, MD*,†; Wang, Ning, PhD*,†,‡; Li, Jing, MD*; Wang, Guangyun, MD*; Seto, Sai Wang, PhD; Chang, Dennis, PhD; Liang, Huazheng, PhD§

Journal of Cardiovascular Pharmacology: May 2019 - Volume 73 - Issue 5 - p 316–325
doi: 10.1097/FJC.0000000000000664
Original Article
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Abstract: Chuanxiong rhizome has been widely used for the treatment of cerebral vascular disease in traditional Chinese medicine. The integrity of blood–brain barrier (BBB) is closely linked to the cerebral vascular disease. The protective effects of ligustilide, the major bioactive component in Chuanxiong rhizome, on cerebral blood vessels have been reported previously, but its effects and potential mechanism on BBB have not been entirely clarified. In the current work, the effects of ligustilide on BBB permeability and the underlying molecular mechanisms had been investigated using the model of BBB established by coculturing astrocytes and brain microvascular endothelial cells isolated from the rat brain. The ischemia-damaged model of BBB has been established with oxygen and glucose deprivation (OGD). Our results indicated that OGD significantly increased the permeability in the coculture BBB model. This OGD-induced increase in permeability could suppress by ligustilide in a concentration-dependent manner. Also, ligustilide promoted both gene and protein expression of tight junction proteins. Ligustilide suppressed the upregulation of HIF-1α, vascular endothelial growth factor, and AQP-4 in the BBB model induced by OGD. Collectively, all results have demonstrated that ligustilide is capable of reducing the permeability of BBB in vitro model induced by OGD through HIF-1α/vascular endothelial growth factor pathway and AQP-4, which provide a new target for the clinical application of ligustilide on BBB after stroke in future.

*Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of Chinese Medicine, Hefei, China;

Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine, Hefei, China;

National Institute of Complementary Medicine, Western Sydney University, Penrith, New South Wales, Australia; and

§Medical School, Western Sydney University, Penrith, New South Wales, Australia.

Reprints: Ning Wang, PhD, Department of Pharmacy, Anhui University of Chinese Medicine, NO.1 Qian Jiang Rd, Hefei 230012, China (e-mail: wnsci123@163.com) or Sipeng Wu, MD (e-mail: wsphefei@163.com).

Supported by the National Natural Science Foundation of China (No. 81773933, 81374005). The key projects of overseas visits of outstanding young backbone talents from universities in Anhui Province (gxfxZD2016117), academic assistance program for the top-notch innovative talents from universities in 2017 provided by Anhui Province Office of Education (gxbjZD15).

The authors report no conflicts of interest.

All authors were involved in the collection and interpretation of data and the writing of the manuscript.

All authors have been personally and actively involved in substantive work leading to the report and will hold themselves jointly and individually responsible for its content; whole research process was approved by the Animal Care and Use Committee of the Anhui University of Chinese Medicine and conformed to the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health. I testify to the accuracy of the aforementioned results on behalf of all the authors.

Received October 23, 2018

Accepted January 28, 2019

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