Biomolecules & Therapeutics  
The Memory-Enhancing Effects of Liquiritigenin by Activation of NMDA Receptors and the CREB Signaling Pathway in Mice
Yong-Hyun Ko1, Seung-Hwan Kwon1, Ji-Young Hwang1, Kyung-In Kim1, Jee-Yeon Seo1, Thi-Lien Nguyen2, Seok-Yong Lee1, Hyoung-Chun Kim3 and Choon-Gon Jang1,*
1Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
2Department of Pharmacology, National Institute of Drug Quality Control, 48-Hai Ba Trung, Ha Noi, Viet Nam
3Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea
E-mail: jang@skku.edu
Tel: +82-31-290-7780, Fax: +82-31-292-8800
Received: December 27, 2016; Revised: February 24, 2017; Accepted: March 8, 2017; Published online: May 30, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ. In addition, the expression of NMDAR subunits 1, 2A, and 2B; postsynaptic density-95 (PSD-95); phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII); phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2); and phosphorylation of cAMP response element binding (CREB) proteins were examined by Western blot. In vivo, we found that treatment with LQ significantly improved memory performance in both behavioral tests. In vitro, LQ significantly increased NMDARs in the hippocampus. Furthermore, LQ significantly increased PSD-95 expression as well as CaMKII, ERK, and CREB phosphorylation in the hippocampus. Taken together, our results suggest that LQ has cognition enhancing activities and that these effects are mediated, in part, by activation of the NMDAR and CREB signaling pathways.
Keywords: Liquiritigenin, Cognition, N-methyl-D-aspartic acid receptor, Postsynaptic density-95, cAMP response element binding


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