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.
J Cardiovasc Pharmacol. 2019 May;73(5):316-325. doi: 10.1097/FJC.0000000000000664.
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.
川芎根茎在中医药中被广泛用于治疗脑血管疾病。血脑屏障 (BBB) 的完整性与脑血管疾病密切相关。先前已有报道称，川芎根茎中的主要生物活性成分藁本内酯对脑血管具有保护作用，但它对 BBB 的作用及其潜在机制尚未完全阐明。在目前的工作中，使用从大鼠脑分离的星形胶质细胞和脑微血管内皮细胞共培养建立的 BBB 模型，研究了藁本内酯对 BBB 通透性的影响及其潜在的分子机制。用氧葡萄糖剥夺 (OGD) 建立了 BBB 缺血损伤模型。结果表明，OGD 显著增加了共培养 BBB 模型的通透性。这种 OGD 诱导的通透性增加可以被藁本内酯浓度依赖性地抑制。此外，藁本内酯还促进了紧密连接蛋白的基因和蛋白表达。藁本内酯抑制了 OGD 诱导的 BBB 模型中 HIF-1α、血管内皮生长因子和 AQP-4 的上调。综上所述，所有结果表明，藁本内酯能够通过 HIF-1α/血管内皮生长因子途径和 AQP-4 降低 OGD 诱导的体外 BBB 模型的通透性，为今后脑卒中后藁本内酯在 BBB 临床应用提供了新的靶点。
