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KMID : 0606920120200010027
Biomolecules & Therapeutics
2012 Volume.20 No. 1 p.27 ~ p.35
Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation: A Possible Role in Neuroprotection
Jeon Se-Jin

Bak Hae-Rang
Seo Jung-Eun
Han So-Min
Lee Sung-Hoon
Han Seol-Heui
Kwon Kyoung-Ja
Ryu Jong-Hoon
Cheong Jae-Hoon
Ko Kwang-Ho
Yang Sung-IL
Choi Ji-Woong
Park Seung-Hwa
Shin Chan-Young
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-3¥â 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.
KEYWORD
Oroxylin A, BDNF, CREB, Adenosine A2A receptor, CGS21680, ZM241385
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