title: Ginkgo biloba Extract (EGb 761®) Inhibits Glutamate-induced Up-regulation of Tissue Plasminogen Activator Through Inhibition of c-Fos Translocation in Rat Primary Cortical Neurons.
abstract: EGb 761(®) , a standardized extract of Ginkgo biloba leaves, has antioxidant and antiinflammatory properties in experimental models of neurodegenerative disorders such as stroke and Alzheimer's disease. Tissue plasminogen activator (tPA) acts a neuromodulator and plays a crucial role in the manifestation of neurotoxicity leading to exaggerated neuronal cell death in neurological insult conditions. In this study, we investigated the effects of EGb 761 on the basal and glutamate-induced activity and expression of tPA in rat primary cortical neurons. Under basal condition, EGb 761 inhibited both secreted and cellular tPA activities, without altering tPA mRNA level, as modulated by the activation of p38. Compared with basal condition, EGb 761 inhibited the glutamate-induced up-regulation of tPA mRNA resulting in the normalization of overt tPA activity and expression. c-Fos is a component of AP-1, which plays a critical role in the modulation of tPA expression. Interestingly, EGb 761 inhibited c-Fos nuclear translocation without affecting c-Fos expression in glutamate-induced rat primary cortical neurons. These results demonstrated that EGb 761 can modulate tPA activity under basal and glutamate-stimulated conditions by both translational and transcriptional mechanisms. Thus, EGb 761 could be a potential and effective therapeutic strategy in tPA-excessive neurotoxic conditions.
authors.affiliation: Department of Neuroscience, Center of Neuroscience Research, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Kyu Suk
authors.initials: KS
authors.lastname: Cho
authors.affiliation: Department of Family Medicine, Brain Korea 21 Project Medical Science, College of Medicine, Korea University, Seoul, Korea.
authors.forename: Ian Myungwon
authors.initials: IM
authors.lastname: Lee
authors.affiliation: Department of Environmental and Tropical Medicine, KU Open Innovation Center, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Seobo
authors.initials: S
authors.lastname: Sim
authors.affiliation: Department of Neuroscience, Center of Neuroscience Research, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Neuroscience, Center of Neuroscience Research, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Edson Luck
authors.initials: EL
authors.lastname: Gonzales
authors.affiliation: Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
authors.affiliation: Department of Pharmacy, College of Pharmacy, Sahmyook University, Seoul, Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Department of Neuroscience, Center of Neuroscience Research, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.affiliation: Department of Neuroscience, Center of Neuroscience Research, Konkuk University School of Medicine, Seoul, Korea.|Department of Neurology, Konkuk University Medical Center, Seoul, Korea.
authors.forename: Kyoung Ja
authors.initials: KJ
authors.lastname: Kwon
authors.affiliation: Department of Neuroscience, Center of Neuroscience Research, Konkuk University School of Medicine, Seoul, Korea.|Department of Neurology, Konkuk University Medical Center, Seoul, Korea.
authors.forename: Seol-Heui
authors.initials: SH
authors.lastname: Han
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D020441:Ginkgo biloba / Q000737:chemistry; D018698:Glutamic Acid / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000096983:Ginkgo Extract
chemical_list: D018698:Glutamic Acid; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D010959:Tissue Plasminogen Activator; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract
keywords: EGb 761®; c-Fos; p38; tPA; translocation