Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation: A Possible Role in Neuroprotection

  • Jeon, Se-Jin (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Bak, Hae-Rang (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Seo, Jung-Eun (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Han, So-Min (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Lee, Sung-Hoon (Neuroscience Research Center, Institute for Advanced Biomedical Sciences, School of Medicine, Konkuk University) ;
  • Han, Seol-Heui (Neuroscience Research Center, Institute for Advanced Biomedical Sciences, School of Medicine, Konkuk University) ;
  • Kwon, Kyoung-Ja (Neuroscience Research Center, Institute for Advanced Biomedical Sciences, School of Medicine, Konkuk University) ;
  • Ryu, Jong-Hoon (Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyunghee University) ;
  • Cheong, Jae-Hoon (Department of Pharmacy, Sahmyook University) ;
  • Ko, Kwang-Ho (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Yang, Sung-Il (Department of Pharmacology, School of Medicine, Konkuk University) ;
  • Choi, Ji-Woong (College of Pharmacy, Gachon University of Medicine and Science) ;
  • Park, Seung-Hwa (Neuroscience Research Center, Institute for Advanced Biomedical Sciences, School of Medicine, Konkuk University) ;
  • Shin, Chan-Young (Neuroscience Research Center, Institute for Advanced Biomedical Sciences, School of Medicine, Konkuk University)
  • Received : 2011.08.24
  • Accepted : 2011.11.02
  • Published : 2012.01.31
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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 $A2_A$ receptor colocalized with BDNF in brain and the functional interaction between $A2_A$ 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 $A2_A$ receptor system. As expected, CGS21680 ($A2_A$ 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-$3{\beta}$ 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 $A2_A$ receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.

Keywords

References

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