Jin Xiaomei, Wang Yamin, Li Xiaojing, Tan Xianxing, Miao Zhigang, Chen Yuanyuan, Hamdy Ronald C, Chua Balvin H L, Kong Jiming, Zhao Heqing, Xu Xingshun
Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, People's Republic of China.
Neurotox Res. 2015 Apr;27(3):268-74. doi: 10.1007/s12640-014-9507-7. Epub 2015 Feb 10.
7,8-Dihydroxy-4-methylcoumarin (Dhmc) is a precursor in the synthesis of derivatives of 4-methyl coumarin, which has excellent radical scavenging properties. In this study, we investigated whether Dhmc protects against oxidative stress and ischemic brain injury. We found that Dhmc protected against glutamate toxicity in hippocampal HT-22 cells in a concentration-dependent manner in vitro. Dhmc inhibited glutamate-induced glutathione depletion and generation of reactive oxygen species, suggesting that Dhmc has an antioxidant effect. In addition, Dhmc inhibited glutamate-induced depletion of hippocalcin, a protein that buffers intracellular calcium and prevents calcium-induced cell death. In our in vivo studies, Dhmc reduced infarct volume in neonatal rats when administered 4 h after cerebral hypoxia/ischemia injury and attenuated the hypoxia/ischemia injury-induced decrease of hippocalcin expression in neonatal rats. Taken together, these results suggest that Dhmc prevents glutamate-induced toxicity by scavenging free radicals and regulating hippocalcin expression. Dhmc may represent a promising agent in the treatment of acute and chronic neurological disorders induced by oxidative stress.
7,8 - 二羟基 - 4 - 甲基香豆素（Dhmc）是4 - 甲基香豆素衍生物合成中的一种前体，其具有出色的自由基清除特性。在本研究中，我们调查了Dhmc是否能抵御氧化应激和缺血性脑损伤。我们发现，在体外，Dhmc以浓度依赖性方式保护海马HT - 22细胞免受谷氨酸毒性作用。Dhmc抑制了谷氨酸诱导的谷胱甘肽耗竭和活性氧的生成，这表明Dhmc具有抗氧化作用。此外，Dhmc抑制了谷氨酸诱导的海马钙结合蛋白的耗竭，海马钙结合蛋白是一种缓冲细胞内钙并防止钙诱导细胞死亡的蛋白质。在我们的体内研究中，在脑缺氧/缺血损伤后4小时给予Dhmc可减少新生大鼠的梗死体积，并减轻缺氧/缺血损伤诱导的新生大鼠海马钙结合蛋白表达的降低。综上所述，这些结果表明Dhmc通过清除自由基和调节海马钙结合蛋白表达来预防谷氨酸诱导的毒性。Dhmc可能是治疗由氧化应激引起的急慢性神经疾病的一种有前景的药物。
