Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Road, Nanjing, Jiangsu 211166, China.
Department of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu 210023, China.
Eur J Pharmacol. 2018 Aug 15;833:221-229. doi: 10.1016/j.ejphar.2018.06.012. Epub 2018 Jun 8.
Ginkgolide K (GK) is a new compound extracted from the leaves of Ginkgo biloba, which has been recognized to exert anti-oxidative stress and neuroprotective effect on ischemic stroke. While whether it plays an enhanced effect on angiogenesis during ischemic stroke remains unknown. The aim of this study was to investigate the effect of ginkgolide K on promoting angiogenesis as well as the protective mechanism after cerebral ischemia-reperfusion. Using the transient middle cerebral artery occlusion (tMCAO) mouse model, we found that GK (3.5, 7.0, 14.0 mg/kg, i.p., bid., 2 weeks) attenuated neurological impairments, and promoted angiogenesis of injured ipsilateral cortex and striatum after 14 days of cerebral ischemia-reperfusion in mice. Further, GK (3.5 mg/kg in vivo, 10 μM in vitro) significantly up-regulated the expressions of HIF-1α and VEGF in tMCAO mouse brains and in b End3 cells after OGD/R, and GK-induced upregulation of HIF-1α and VEGF in b End3 cells could be abolished by JAK2/STAT3 inhibitor AG490. Our results demonstrate that GK promotes angiogenesis after ischemia stroke through increasing the expression of HIF-1α/VEGF via JAK2/STAT3 pathway, which provide an insight into the novel clinical application of GK and its analogs in ischemic stroke therapy in future.
白果内酯 K（GK）是从银杏叶中提取的一种新化合物，已被证明对缺血性中风具有抗氧化应激和神经保护作用。然而，它是否对缺血性中风期间的血管生成具有增强作用尚不清楚。本研究旨在探讨白果内酯 K 对促进血管生成的作用及其在脑缺血再灌注后的保护机制。使用短暂性大脑中动脉闭塞（tMCAO）小鼠模型，我们发现 GK（3.5、7.0、14.0mg/kg，腹腔注射，每天两次，持续 2 周）可减轻神经损伤，并促进缺血再灌注后 14 天小鼠损伤侧皮质和纹状体的血管生成。此外，GK（体内 3.5mg/kg，体外 10μM）可显著上调 tMCAO 小鼠大脑和 OGD/R 后 bEnd3 细胞中的 HIF-1α 和 VEGF 的表达，而 GK 诱导的 bEnd3 细胞中 HIF-1α 和 VEGF 的上调可被 JAK2/STAT3 抑制剂 AG490 所抑制。我们的结果表明，GK 通过增加 HIF-1α/VEGF 的表达来促进缺血性中风后的血管生成，这为 GK 及其类似物在缺血性中风治疗中的新的临床应用提供了新的思路。
