title: Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation: A Possible Role in Neuroprotection.
abstract: Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine A2A receptor colocalized with BDNF in brain and the functional interaction between A2A receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of A2A receptor system. As ex-pected, CGS21680 (A2A receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-3β signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through A2A receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 ; Neuroscience Research Center, Institute for Advanced Biomedical Sciences.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Haerang
authors.initials: H
authors.lastname: Bak
authors.forename: Jungeun
authors.initials: J
authors.lastname: Seo
authors.forename: So Min
authors.initials: SM
authors.lastname: Han
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seol-Heui
authors.initials: SH
authors.lastname: Han
authors.forename: Kyoung Ja
authors.initials: KJ
authors.lastname: Kwon
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Yang
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: Seung Hwa
authors.initials: SH
authors.lastname: Park
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
keywords: Adenosine A2A receptor; BDNF; CGS21680; CREB; Oroxylin A; ZM241385