title: The protective role of (-)-epigallocatechin-3-gallate in thrombin-induced neuronal cell apoptosis and JNK-MAPK activation.
abstract: (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has anti-inflammatory and antioxidant properties and provides neuroprotection against central nervous system diseases. Yet, it is not known whether EGCG may be neuroprotective against intracerebral hemorrhage. In this study, we used a simplified in-vitro model of thrombin neurotoxicity to test whether EGCG provides neuroprotection against thrombin-associated toxicity. Exposure of primary cortical neurons to thrombin (100 U/ml) caused dose-dependent and time-dependent cytotoxicity. Cell Counting Kit 8 and lactate dehydrogenase were used to monitor cell viability after exposure of neurons to thrombin or EGCG and after EGCG pretreatment. Flow cytometric analysis and western blotting demonstrated that thrombin-induced neuron degeneration occurs through apoptosis. A concentration of 25 μM EGCG significantly abolished thrombin-induced toxicity and prevented apoptosis by suppressing c-Jun-N-terminal kinase (JNK) phosphorylation, and the JNK inhibitor SP600125 reduced thrombin-induced caspase 3 activation and apoptosis. These data suggest that EGCG may have protective effects against thrombin-induced neuroapoptosis by inhibiting the activation of JNK, leading to caspase 3 cleavage. EGCG is a novel candidate neuroprotective agent against intracerebral hemorrhage-induced neurotoxicity.
authors.affiliation: aDepartment of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China bUniversity of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Zimering
authors.forename: Kun
authors.initials: K
authors.lastname: Zan
authors.forename: Zuohui
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Shi
authors.forename: Jie
authors.initials: J
authors.lastname: Zu
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Hua
authors.forename: Xinchun
authors.initials: X
authors.lastname: Ye
authors.forename: Guiyun
authors.initials: G
authors.lastname: Cui
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D013917:Thrombin / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; C432165:pyrazolanthrone; D002392:Catechin; C045651:epigallocatechin gallate; D007770:L-Lactate Dehydrogenase; D048670:MAP Kinase Kinase 4; D013917:Thrombin; C505410:Casp3 protein, rat; D053148:Caspase 3
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