The flavonoid baicalein promotes NMDA receptor-dependent long-term potentiation and enhances memory.
OBJECTIVE
There is growing interest in the physiological functions of flavonoids, especially in their effects on cognitive function and on neurodegenerative diseases. The aim of the current investigation was to evaluate the role of the flavonoid baicalein in long-term potentiation (LTP) in the hippocampal CA1 region and cognitive behavioural performance.


METHODS
Effects of baicalein on LTP in rat hippocampal slices were investigated by electrophysiological methods. Phosphorylation of Akt (at Ser(473)), the extracellular signal-regulated kinase (ERK1/2) and the transcription factor cAMP response element-binding protein (CREB) (at Ser(133)) were analysed by Western blot. Fear conditioning was used to determine whether baicalein could improve learning and memory in rats.


RESULTS
Baicalein enhanced the N-methyl-d-aspartate glutamate receptor-dependent LTP in a bell-shaped concentration-dependent manner. Addition of the lipoxygenase metabolites 12(S)-HETE and 12(S)-HPETE did not reverse these effects of baicalein. Baicalein treatment enhanced phosphorylation of Akt during induction of LTP with the same bell-shaped dose-response curve. LTP potentiation induced by baicalein was blocked by inhibitors of phosphoinositide 3-kinase. CREB phosphorylation was also increased in the CA1 region of baicalein-treated slices. Baicalein-treated rats performed significantly better than controls in a hippocampus-dependent contextual fear conditioning task. Furthermore, baicalein treatment selectively increased the phosphorylation of Akt and CREB in the CA1 region of hippocampus, but not in the prefrontal cortex, after fear conditioning training.


CONCLUSIONS
Our results demonstrate that the flavonoid baicalein can facilitate memory, and therefore it might be useful in the treatment of patients with memory disorders.
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Wei
W
Wang
Fang
F
Wang
Yuan-Jian
YJ
Yang
Zhuang-Li
ZL
Hu
Li-Hong
LH
Long
Hui
H
Fu
Na
N
Xie
Jian-Guo
JG
Chen
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects*; D003214:Conditioning, Classical; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D000975:Antioxidants; D017362:Cyclic AMP Response Element-Binding Protein; D044950:Flavanones; D016859:Lipoxygenase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; C006680:baicalein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt