Zhang Yehao, Liu Jianxun, Yang Bin, Zheng Yongqiu, Yao Mingjiang, Sun Mingqian, Xu Li, Lin Chengren, Chang Dennis, Tian Fangze
Beijing Key Laboratory of Pharmacology of Chinese Materia Region, Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
National Institute of Complementary Medicine, Western Sydney University, Penrith, NSW, Australia.
Front Pharmacol. 2018 May 16;9:518. doi: 10.3389/fphar.2018.00518. eCollection 2018.
Astrogliosis has the potential to lead to harmful effects, namely, neuroinflammation, and to interfere with synapse sprouting. Previous studies have suggested that Lipocalin-2 (LCN2) acts as a key target in regulating the reaction of astrocytes. However, the underlying molecular mechanism is not fully elucidated. In the present study, we examined the neuroprotective and anti-inflammatory effects of extract (EGB), a well-known extract with potential immunoregulatory properties in the nervous system. Triphenyltetrazolium chloride staining, hematoxylin-eosin staining, electron microscopy, and neurological assessments were performed in a microsphere-embolized rat model. Human astrocytes exposed to oxygen glucose deprivation (OGD) were used for experiments. Inflammatory cytokines, multi-labeling immunofluorescence, and Western blotting were used to investigate the molecular mechanisms underlying the EGB-mediated anti-inflammatory effects and . EGB markedly attenuated cerebral infarction and neuronal apoptosis, reduced the inflammatory cytokine level, and alleviated neurological deficiencies in cerebral ischemic rats. After surgery, EGB significantly inhibited astrocyte activation, reduced the phosphorylation of STAT3 and JAK2 and decreased LCN2 expression. , EGB blocked OGD-induced STAT3 activation and the generation of pro-inflammatory cytokines in human astrocytes, and these effects were significantly enhanced by LCN2 overexpression. EGB downregulated these effects enhanced by LCN2 overexpression. EGB is demonstrated to mediate neuroinflammation, which protects against ischemic brain injury by inhibiting astrogliosis and suppresses neuroinflammation via the LCN2-JAK2/STAT3 pathway, providing insight into a promising therapeutic strategy for ischemic stroke.
星形胶质细胞增生有可能导致有害影响，即神经炎症，并干扰突触萌发。先前的研究表明，脂质运载蛋白2（LCN2）是调节星形胶质细胞反应的关键靶点。然而，其潜在的分子机制尚未完全阐明。在本研究中，我们检测了银杏叶提取物（EGB）的神经保护和抗炎作用，EGB是一种在神经系统中具有潜在免疫调节特性的著名提取物。在微球栓塞大鼠模型中进行了氯化三苯基四氮唑染色、苏木精-伊红染色、电子显微镜检查和神经学评估。将暴露于氧葡萄糖剥夺（OGD）的人星形胶质细胞用于实验。使用炎性细胞因子、多标记免疫荧光和蛋白质印迹法来研究EGB介导的抗炎作用的潜在分子机制。EGB显著减轻了脑梗死和神经元凋亡，降低了炎性细胞因子水平，并改善了脑缺血大鼠的神经功能缺损。手术后，EGB显著抑制星形胶质细胞活化，降低STAT3和JAK2的磷酸化水平，并降低LCN2表达。此外，EGB阻断了OGD诱导的人星形胶质细胞中STAT3的活化和促炎细胞因子的产生，而LCN2过表达显著增强了这些作用。EGB下调了LCN2过表达增强的这些作用。结果表明，EGB通过抑制星形胶质细胞增生介导神经炎症，从而对缺血性脑损伤起到保护作用，并通过LCN2-JAK2/STAT3途径抑制神经炎症，为缺血性中风提供了一种有前景的治疗策略。
