Le Jingyang, Xiao Xiao, Zhang Difan, Feng Yi, Wu Zhuoying, Mao Yuechun, Mou Chenye, Xie Yanfei, Chen Xiaowei, Liu Hao, Cui Wei
Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo 315211, China.
Pharmaceuticals (Basel). 2022 Aug 18;15(8):1018. doi: 10.3390/ph15081018.
Ischemic stroke leads to hypoxia-induced neuronal death and behavioral abnormity, and is a major cause of death in the modern society. However, the treatments of this disease are limited. Brilliant Blue FCF (BBF) is an edible pigment used in the food industry that with multiple aromatic rings and sulfonic acid groups in its structure. BBF and its derivatives were proved to cross the blood-brain barrier and have advantages on the therapy of neuropsychiatric diseases. In this study, BBF, but not its derivatives, significantly ameliorated chemical hypoxia-induced cell death in HT22 hippocampal neuronal cell line. Moreover, protective effects of BBF were attributed to the inhibition of the extracellular regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK3β) pathways as evidenced by Western blotting analysis and specific inhibitors. Furthermore, BBF significantly reduced neurological and behavioral abnormity, and decreased brain infarct volume and cerebral edema induced by middle cerebral artery occlusion/reperfusion (MCAO) in rats. MCAO-induced increase of p-ERK in ischemic penumbra was reduced by BBF in rats. These results suggested that BBF prevented chemical hypoxia-induced otoxicity and MCAO-induced behavioral abnormity via the inhibition of the ERK and GSK3β pathways, indicating the potential use of BBF for treating ischemic stroke.
缺血性中风会导致缺氧诱导的神经元死亡和行为异常，是现代社会主要的死亡原因之一。然而，这种疾病的治疗方法有限。亮蓝FCF（BBF）是一种食品工业中使用的可食用色素，其结构中含有多个芳香环和磺酸基团。BBF及其衍生物已被证明可穿过血脑屏障，在神经精神疾病治疗方面具有优势。在本研究中，BBF而非其衍生物能显著改善化学缺氧诱导的HT22海马神经元细胞系细胞死亡。此外，蛋白质免疫印迹分析和特异性抑制剂证明，BBF的保护作用归因于对细胞外调节蛋白激酶（ERK）和糖原合酶激酶-3β（GSK3β）通路的抑制。此外，BBF显著减轻大鼠大脑中动脉闭塞/再灌注（MCAO）诱导的神经和行为异常，并减小脑梗死体积和脑水肿。BBF可降低大鼠MCAO诱导的缺血半暗带中p-ERK的增加。这些结果表明，BBF通过抑制ERK和GSK3β通路预防化学缺氧诱导的毒性和MCAO诱导的行为异常，提示BBF在治疗缺血性中风方面具有潜在用途。
