7,8-Dihydroxy-4-methylcoumarin provides neuroprotection by increasing hippocalcin expression.
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.
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.
Xiaomei
X
Jin
Yamin
Y
Wang
Xiaojing
X
Li
Xianxing
X
Tan
Zhigang
Z
Miao
Yuanyuan
Y
Chen
Ronald C
RC
Hamdy
Balvin H L
BH
Chua
Jiming
J
Kong
Heqing
H
Zhao
Xingshun
X
Xu
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D020520:Brain Infarction / Q000188:drug therapy; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000633:toxicity; D051597:Hippocalcin / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
C114368:7,8-dihydroxy-4-methylcoumarin; D000975:Antioxidants; D003374:Coumarins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D051597:Hippocalcin; D018698:Glutamic Acid