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Oroxylin A increases BDNF production by activation of MAPK-CREB pathway in rat primary cortical neuronal culture.
MedLine Citation:
PMID:  21145362     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Oroxylin A (5,7-dihydroxy-6-methoxyfavone) is a flavonoid compound originated from the root of Scutellaria baicalensis Georgi. Our previous reports suggested that oroxylin A improves memory function in rat, at least in part, by its antagonistic effects on GABA(A) receptor. In addition, oroxylin A protects neurons from ischemic damage by mechanisms currently not clear. In this study we determined whether oroxylin A modulates the level of brain derived neurotrophic factor (BDNF) in primary rat cortical neuronal culture, which is well known for its role on neuronal survival, neurogenesis, differentiation of neurons and synapses and learning and memory. Treatment of oroxylin A for 3-48h increased BDNF expression which was analyzed by ELISA assay and Western blot analysis. Oroxylin A induced slow but sustained increases in intracellular calcium level and activated ERK1/2 mitogen activated protein kinase (MAPK). In addition, oroxylin A phosphorylated cyclic AMP response element binding protein (CREB) at Ser 133 in concentration and time dependent manner. Pretreatment with the MAPK inhibitor PD98059 (10μM) attenuated phosphorylation of ERK1/2 and CREB as well as BDNF production, which suggests that oroxylin A regulates BDNF production by activating MAPK-CREB pathway. GABA(A) antagonist bicuculline mimicked the effects of oroxylin A on BDNF production as well as MAPK-CREB pathway. Increase in intracellular Ca(2+) concentration, phosphorylation of ERK1/2 and CREB, and BDNF expression by oroxylin A was blocked by NMDA receptor inhibitor MK-801 (10μM) as well as tetrodotoxin (TTX, 0.5 and 1μM). The results from the present study suggest that the calcium and p-CREB dependent induction of BDNF expression, possibly via activation of synaptic NMDA receptor through the blockade of GABA(A) activity in cortical neuronal circuitry, might be responsible for the neuroprotective or memory enhancing effects of oroxylin A.
Authors:
Se Jin Jeon; So Young Rhee; Jung Eun Seo; Hae Rang Bak; Sung Hoon Lee; Jong Hoon Ryu; Jae Hoon Cheong; Chan Young Shin; Gun-Hee Kim; Yong Soo Lee; Kwang Ho Ko
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-8
Journal Detail:
Title:  Neuroscience research     Volume:  -     ISSN:  1872-8111     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8500749     Medline TA:  Neurosci Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ireland Ltd.
Affiliation:
Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
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