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 ...
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 $Ca^{2+}$/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.
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 $Ca^{2+}$/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.
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제안 방법
, consecutive entry sequences of ABC, CAB, or BCA but not BAB) and the number of arm entries were manually recorded for each mouse over an 8-min period. One hour before each test, the mice were given LQ (5 or 20 mg/kg, p.o.) or vehicle (10% tween 80 with 5% DMSO in distilled water) for the control group. Percentage alternation was calculated according to the following equation: Percentage alternation=[(Number of alternations)/(Total arm entries-2)]×100.
A 50-W lamp positioned 1 m above both chambers illuminated the apparatus. The mice underwent two separate trials, a training trial and a test trial 24 h later. One hour before the training trial, mice were given LQ (5 or 20 mg/kg, p.
The present study was designed to assess the effects of LQ on learning and memory in normal mice by using the Y-maze and passive avoidance tests. We also confirmed the effects of LQ on biochemical markers in the NMDA signaling pathway, expression of NMDARs (subunits 1, 2A, and 2B), PSD-95 and CaMKII, ERK, and CREB phosphorylation in the hippocampus.
Therefore, in the present study, we investigated whether LQ improved learning and memory in mice. To assess the cognitive-enhancing effects of LQ in mice, we evaluated the effect of LQ on learning and memory with the Y-maze and passive avoidance tests. We also conducted Western blot analysis to test whether LQ affected the NMDAR or cAMP response element binding (CREB) signaling pathways in mouse hippocampus.
To evaluate the effects of LQ on learning and memory, Ymaze and passive avoidance behavioral tests were performed after LQ was administered. Spontaneous alternation behavior in the Y-maze test is a surrogate measure of short-term and working memory (Kwon et al.
대상 데이터
Anti-β-actin antibody and dimethyl sulfoxide (DMSO) were purchased from Sigma Chemicals (St. Louis, MO, USA).
데이터처리
, San Diego, CA, USA). Data from the Y-maze and passive avoidance tests were analyzed with one-way analysis of variance (ANOVA) followed by Newman-Keuls test. Western blot data were analyzed with an unpaired t-test.
성능/효과
In conclusion, our study showed that administering LQ enhanced cognitive performance, which may have resulted from activated signaling by NMDARs and PSD-95 as well as CaMKII, ERK, and CREB phosphorylation in mouse hippocampi. Therefore, our results suggest that cognitive enhancement by LQ may be a candidate for treating cognitive dysfunction in neurological disorders such as AD.
참고문헌 (43)
Aamodt SM Constantine-Paton M 1999 The role of neural activity in synaptic development and its implications for adult brain function Adv Neurol 79 133 144 10514810
Armano S Rossi P Taglietti V D’Angelo E 2000 Long-term potentiation of intrinsic excitability at the mossy fiber-granule cell synapse of rat cerebellum J Neurosci 20 5208 5216 10884304
Barki-Harrington L Elkobi A Tzabary T Rosenblum K 2009 Tyrosine phosphorylation of the 2B subunit of the NMDA receptor is necessary for taste memory formation J Neurosci 29 9219 9226 10.1523/JNEUROSCI.5667-08.2009 19625512
Easton AC Lucchesi W Mizuno K Fernandes C Schumann G Giese KP Müller CP 2013 αCaMKII autophosphorylation controls the establishment of alcohol-induced conditioned place preference in mice Behav Brain Res 252 72 76 10.1016/j.bbr.2013.05.045 23732653
Fleischmann A Hvalby O Jensen V Strekalova T Zacher C Layer LE Kvello A Reschke M Spanagel R Sprengel R Wagner EF Gass P 2003 Impaired long-term memory and NR2A-type NMDA receptor-dependent synaptic plasticity in mice lacking c-Fos in the CNS J Neurosci 23 9116 9122 14534245
Goodfellow MJ Abdulla KA Lindquist DH 2016 Neonatal Ethanol Exposure impairs trace fear conditioning and alters NMDA receptor subunit expression in adult male and female rats Alcohol Clin Exp Res 40 309 318 10.1111/acer.12958 26842250
Gong Y Lippa CF 2010 Review: disruption of the postsynaptic density in Alzheimer’s disease and other neurodegenerative dementias Am J Alzheimers Dis Other Demen 25 547 555 10.1177/1533317510382893 2976708 --> 20858652
Griffith TN Varela-Nallar L Dinamarca MC Inestrosa NC 2010 Neurobiological effects of Hyperforin and its potential in Alzheimer’s disease therapy Curr Med Chem 17 391 406 10.2174/092986710790226156 20015041
Jensen C Forlini C Partridge B Hall W 2016 Australian university students’ coping strategies and use of pharmaceutical stimulants as cognitive enhancers Front Psychol 7 277 10.3389/fpsyg.2016.00277 26973573
Kang HE Jung HY Cho YK Kim SH Sohn SI Baek SR Lee MG 2009 Pharmacokinetics of liquiritigenin in mice, rats, rabbits, and dogs, and animal scale-up J Pharm Sci 98 4327 4342 10.1002/jps.21702 19226634
Kumar NS Nisha N 2014 Phytomedicines as potential inhibitors of beta amyloid aggregation: significance to Alzheimer’s disease Chin J Nat Med 12 801 818 25480511
Kwon SH Hong SI Ma SX Lee SY Jang CG 2015 3′,4′,7-Trihydroxyflavone prevents apoptotic cell death in neuronal cells from hydrogen peroxide-induced oxidative stress Food Chem Toxicol 80 41 51 10.1016/j.fct.2015.02.014 25720812
Kwon SH Ma SX Joo HJ Lee SY Jang CG 2013 Inhibitory effects of Eucommia ulmoides Oliv. Bark on scopolamine-induced learning and memory deficits in mice Biomol. Ther. (Seoul) 21 462 469 10.4062/biomolther.2013.074 24404337
Lai Q Hu P Li Q Li X Yuan R Tang X Wang W Li X Fan H Yin X 2016 NMDA receptors promote neurogenesis in the neonatal rat subventricular zone following hypoxicischemic injury Mol Med Rep 13 206 212 10.3892/mmr.2015.4501 26548659
Lee E Choi SY Yang JH Lee YJ 2016 Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway Korean J Physiol Pharmacol 20 399 406 10.4196/kjpp.2016.20.4.399 4930908 --> 27382356
Liu RT Tang JT Zou LB Fu JY Lu QJ 2011 Liquiritigenin attenuates the learning and memory deficits in an amyloid protein precursor transgenic mouse model and the underlying mechanisms Eur J Pharmacol 669 76 83 10.1016/j.ejphar.2011.07.051 21872584
Liu RT Zou LB Fu JY Lu QJ 2010 Effects of liquiritigenin treatment on the learning and memory deficits induced by amyloid beta-peptide (25–35) in rats Behav Brain Res 210 24 31 10.1016/j.bbr.2010.01.041 20117143
Liu RT Zou LB Lu QJ 2009 Liquiritigenin inhibits Aβ 25–35 -induced neurotoxicity and secretion of Aβ 1–40 in rat hippocampal neurons Acta Pharmacol Sin 30 899 906 10.1038/aps.2009.74 4006661 --> 19574995
Morris RG Anderson E Lynch GS Baudry M 1986 Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5 Nature 319 774 776 10.1038/319774a0 2869411
Nakazawa K McHugh TJ Wilson MA Tonegawa S 2004 NMDA receptors, place cells and hippocampal spatial memory Nat Rev Neurosci 5 361 372 10.1038/nrn1385 15100719
Ortega-Martinez S 2015 A new perspective on the role of the CREB family of transcription factors in memory consolidation via adult hippocampal neurogenesis Front Mol Neurosci 8 46 10.3389/fnmol.2015.00046 4549561 --> 26379491
Oskouei DS Rikhtegar R Hashemilar M Sadeghi-Bazargani H Sharifi-Bonab M Sadeghi-Hokmabadi E Zarrintan S Sharifipour E 2013 The effect of Ginkgo biloba on functional outcome of patients with acute ischemic stroke: a double-blind, placebo-controlled, randomized clinical trial J Stroke Cerebrovasc Dis 22 e557 e563 10.1016/j.jstrokecerebrovasdis.2013.06.010 23871729
Qin RA Yao XX Huang ZY 2012 Effects of compound danshen tablets on spatial cognition and expression of brain beta-amyloid precursor protein in a rat model of Alzheimer’s disease J Tradit Chin Med 32 63 66 10.1016/S0254-6272(12)60033-8 22594104
Rajendran PR Thompson RE Reich SG 2001 The use of alternative therapies by patients with Parkinson’s disease Neurology 57 790 794 10.1212/WNL.57.5.790 11552005
Ruscheweyh R Wilder-Smith O Drdla R Liu XG SandKühler J 2011 Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy Mol Pain 7 20 10.1186/1744-8069-7-20 3078873 --> 21443797
Shimizu E Tang YP Rampon C Tsien JZ 2000 NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation Science 290 1170 1174 10.1126/science.290.5494.1170 11073458
Song JC Seo MK Park SW Lee JG Kim YH 2016 Differential effects of olanzapine and haloperidol on mk-801-induced memory impairment in mice Clin Psychopharmacol Neurosci 14 279 285 10.9758/cpn.2016.14.3.279 4977819 --> 27489382
Stan TL Sousa VC Zhang X Ono M Svenningsson P 2015 Lurasidone and fluoxetine reduce novelty-induced hypophagia and NMDA receptor subunit and PSD-95 expression in mouse brain Eur Neuropsychopharmacol 25 1714 1722 10.1016/j.euroneuro.2015.07.007 26256011
Stranahan AM Mattson MP 2010 Selective vulnerability of neurons in layer II of the entorhinal cortex during aging and Alzheimer’s disease Neural Plast 2010 108190 10.1155/2010/108190 21331296
Tang M Wang Z Zhou Y Xu W Li S Wang L Wei D Qiao Z 2013 A novel drug candidate for Alzheimer’s disease treatment: gx-50 derived from Zanthoxylum bungeanum J Alzheimers Dis 34 203 213 23186988
Vaynman S Ying Z Gomez-Pinilla F 2004 Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition Eur J Neurosci 20 2580 2590 10.1111/j.1460-9568.2004.03720.x 15548201
Veroniki AA Straus SE Ashoor HM Hamid JS Hemmelgarn BR Holroyd-Leduc J Majumdar SR McAuley G Tricco AC 2016 Comparative safety and effectiveness of cognitive enhancers for Alzheimer’s dementia: protocol for a systematic review and individual patient data network meta-analysis BMJ Open 6 e010251 10.1136/bmjopen-2015-010251
Wei F Wang GD Zhang C Shokat KM Wang H Tsien JZ Liauw J Zhuo M 2006 Forebrain overexpression of CaMKII abolishes cingulate long term depression and reduces mechanical allodynia and thermal hyperalgesia Mol Pain 2 21 10.1186/1744-8069-2-21 1513196 --> 16776832
Xu M Chandler LJ Woodward JJ 2008 Ethanol inhibition of recombinant NMDA receptors is not altered by coexpression of CaMKII-alpha or CaMKII-beta Alcohol 42 425 432 10.1016/j.alcohol.2008.04.007 2629600 --> 18562151
Yamada K Shimizu M Kawabe K Ichitani Y 2015 Hippocampal AP5 treatment impairs both spatial working and reference memory in radial maze performance in rats Eur J Pharmacol 758 137 141 10.1016/j.ejphar.2015.03.080 25863255
Zhao B Wang Y Li Y Qiao X Yan P Zhu Y Lai J 2015 Differential phosphorylation of NMDAR1-CaMKII-MAPKs in the rat nucleus accumbens following chronic ethanol exposure Neurosci Lett 597 60 65 10.1016/j.neulet.2015.03.061 25837445
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