Department of Neurology and Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, Jiangsu, People's Republic of China.
Neurochem Res. 2014 Feb;39(2):269-75. doi: 10.1007/s11064-013-1218-6. Epub 2013 Dec 17.
Daphnetin (DAP), a coumarin derivative, has been reported to have multiple pharmacological actions including analgesia, antimalarial, anti-arthritic, and anti-pyretic properties. It is unclear whether DAP has neuroprotective effects on ischemic brain injury. In this study, we found that DAP treatment (i.c.v.) reduced the infarct volume at 24 h after ischemia/reperfusion injury and improved neurological behaviors in a middle cerebral artery occlusion mouse model. Moreover, we provided evidences that DAP had protective effects on infarct volume in neonate rats even it was administrated at 4 h after cerebral hypoxia/ischemia injury. To explore its neuroprotective mechanisms of DAP, we examined the protection of DAP on glutamate toxicity-induced cell death in hippocampal HT-22 cells. Our results demonstrated that DAP protected against glutamate toxicity in HT-22 cells in a concentration-dependent manner. Further, we found that DAP maintained the cellular levels of glutathione and superoxide dismutase activity, suggesting the anti-oxidatant activity of DAP. Since DAP has been used for the treatment of coagulation disorder and rheumatoid arthritis for long time with a safety profile, DAP will be a promising agent for the treatment of stroke.
瑞香素（DAP）是香豆素的衍生物，具有多种药理作用，包括镇痛、抗疟、抗关节炎和退热作用。目前尚不清楚 DAP 是否对缺血性脑损伤具有神经保护作用。在这项研究中，我们发现 DAP 治疗（侧脑室注射）可减少缺血/再灌注损伤后 24 小时的梗死体积，并改善大脑中动脉闭塞小鼠模型的神经行为。此外，我们提供的证据表明，即使在脑缺氧/缺血损伤后 4 小时给予 DAP，它也对新生儿大鼠的梗死体积具有保护作用。为了探讨 DAP 的神经保护机制，我们研究了 DAP 对海马 HT-22 细胞中谷氨酸毒性诱导的细胞死亡的保护作用。结果表明，DAP 以浓度依赖的方式保护 HT-22 细胞免受谷氨酸毒性。此外，我们发现 DAP 维持了细胞内谷胱甘肽水平和超氧化物歧化酶活性，表明 DAP 具有抗氧化活性。由于 DAP 长期以来一直用于治疗凝血障碍和类风湿性关节炎，且具有良好的安全性，因此 DAP 将成为治疗中风的有前途的药物。
