title: Neuroprotective effect of osthole against oxygen and glucose deprivation in rat cortical neurons: involvement of mitogen-activated protein kinase pathway.
abstract: Osthole, a bioactive simple coumarin derivative extracted from many medicinal plants such as Cnidium monnieri (L.) Cusson, exerts a broad spectrum of pharmacological activities and is considered to have potential therapeutic applications. The aim of this study was to investigate the potential neuroprotective role of osthole against ischemic injury in vitro, as well as the potential mechanism. Cultured cortical neurons were exposed to oxygen and glucose deprivation (OGD) for 4 h followed by a 24 h reperfusion. Osthole exhibited remarkable neuroprotection in a dose-dependent manner and the effect required presence of osthole during both OGD and reperfusion phases. Western blot was used to examine the activation of three members of mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 kinase (p38). We found that osthole prolonged activation of ERK1/2 and prevented activation of JNK. Furthermore, we investigated the effects of MAPKs inhibitors on osthole-induced protection. The results demonstrated that the protection of osthole was partly reversed by PD98059, a selective inhibitor of ERK1/2, but further enhanced by the JNK inhibitor SP600125. In addition, osthole-induced reduction of neuronal apoptosis was abrogated by the ERK1/2 inhibitor PD98059, whereas the total neuronal death was further decreased by the JNK inhibitor SP600125. In summary, these data suggested that osthole had neuroprotective effect against ischemic injury in vitro, and the protection possibly was associated with prolonged activation of ERK1/2 and suppression of JNK activity.
authors: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors: T
authors: T
authors: Chen
authors: W
authors: W
authors: Liu
authors: X
authors: X
authors: Chao
authors: Y
authors: Y
authors: Qu
authors: L
authors: L
authors: Zhang
authors: P
authors: P
authors: Luo
authors: K
authors: K
authors: Xie
authors: J
authors: J
authors: Huo
authors: Z
authors: Z
authors: Fei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003374:Coumarins / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D015424:Reperfusion; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D007770:L-Lactate Dehydrogenase; D020928:Mitogen-Activated Protein Kinases; C022616:thiazolyl blue; D005947:Glucose; C046627:osthol