title: Baicalin attenuates oxygen-glucose deprivation-induced injury via inhibiting NMDA receptor-mediated 5-lipoxygenase activation in rat cortical neurons.
abstract: The flavonoid baicalin exerts neuroprotective effects but the mechanism is not fully clarified. On the other hand, 5-lipoxygenase (5-LOX) activation is involved in ischemic neuronal injury. In this study, we determined whether baicalin protects rat cortical neurons against oxygen-glucose deprivation (OGD)-induced ischemic-like injury, if so, whether this effect relates to 5-LOX activation. After the neurons were injured by 1.5-h OGD and 24-h recovery, their viability reduced and necrosis occurred; these injuries were attenuated by baicalin (1 and 5microM) as well as caffeic acid (a 5-LOX inhibitor, 5 and 25microM) and MK-801 (an NMDA receptor antagonist, 1-10microM). OGD-induced 5-LOX translocation to the nuclear envelope as detected by immunoblotting, immunocytochemistry and 5-LOX transfection; this translocation was inhibited by baicalin (5microM) and MK-801 (5microM) but not by caffeic acid (5microM). During 0.5- to 2-h recovery after 1.5-h OGD, the production of 5-LOX metabolites, cysteinyl leukotrienes, was increased; this increased production was inhibited by baicalin and MK-801, while both the increased and baseline production were inhibited by caffeic acid. In addition baicalin and MK-801, not caffeic acid, inhibited glutamate-induced elevation of intracellular calcium. These results indicate that baicalin attenuates ischemic-like injury in the neurons, and this effect partly relates to the inhibition of NMDA receptor-mediated 5-LOX activation.
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, 388, Yu Hang Tang Road, Hangzhou 310058, China.
authors.forename: Qiu-Fu
authors.initials: QF
authors.lastname: Ge
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.forename: Zhen-Qiu
authors.initials: ZQ
authors.lastname: Ma
authors.forename: Jian-Ren
authors.initials: JR
authors.lastname: Liu
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.forename: Er-Qing
authors.initials: EQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003545:Cysteine / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D007120:Immunochemistry; D015289:Leukotrienes / Q000378:metabolism; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014162:Transfection
chemical_list: D005419:Flavonoids; D015289:Leukotrienes; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C112381:cysteinyl-leukotriene; C038044:baicalin; D001094:Arachidonate 5-Lipoxygenase; D005947:Glucose; D003545:Cysteine