Exploring the Effect of Ginsenoside Rh1 in a Sleep Deprivation‐Induced Mouse Memory Impairment Model

Panax ginseng C.A. Meyer (Araliaceae) has been used in traditional Chinese medicine for enhancing cognition for thousands of years. Ginsenoside Rh1, a constituent of ginseng root, as with other constituents, has memory‐improving effects in normal mice and scopolamine‐induced amnesic mice. Sleep deprivation (SD) is associated with memory impairment through induction of oxidative stress. The present study investigated the effect of Rh1 against SD‐induced cognitive impairment and attempted to define the possible mechanisms involved. Ginsenoside Rh1 (20 μmol/kg; 40 μmol/kg) and modafinil (0.42 g/kg) were administered to the mice intraperitoneally for 23 days. After 14‐day SD, locomotor activity was examined using the open field test, and the object location recognition and Morris water maze tests were used to evaluate cognitive ability. The cortex and hippocampus were then dissected and homogenized, and levels and activities of antioxidant defense biomarkers were evaluated to determine the level of oxidative stress. The results revealed that Rh1 prevented cognitive impairment induced by SD, and its ability to reduce oxidative stress in cortex and hippocampus may contribute to the mechanism of action. Copyright © 2017 John Wiley & Sons, Ltd.

[1]  I. Alhaider,et al.  The beneficial effects of regular exercise on cognition in REM sleep deprivation: Behavioral, electrophysiological and molecular evidence , 2012, Neurobiology of Disease.

[2]  J. Delacour,et al.  A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data , 1988, Behavioural Brain Research.

[3]  M. Minzenberg,et al.  Modafinil: A Review of Neurochemical Actions and Effects on Cognition , 2008, Neuropsychopharmacology.

[4]  H. Roffwarg,et al.  Rapid eye movement sleep deprivation decreases long-term potentiation stability and affects some glutamatergic signaling proteins during hippocampal development , 2008, Neuroscience.

[5]  F. Gomez-Pinilla,et al.  Vitamin E Protects Against Oxidative Damage and Learning Disability After Mild Traumatic Brain Injury in Rats , 2010, Neurorehabilitation and neural repair.

[6]  Donna H. Ryan,et al.  Sleep Deprivation by the “Flower Pot” Technique and Spatial Reference Memory , 1997, Physiology & Behavior.

[7]  Y. Khadrawy,et al.  Effect of oxidative stress induced by paradoxical sleep deprivation on the activities of Na+, K+-ATPase and acetylcholinesterase in the cortex and hippocampus of rat. , 2011, Translational research : the journal of laboratory and clinical medicine.

[8]  K. Brady,et al.  Cognitive enhancers in the treatment of substance use disorders: Clinical evidence , 2011, Pharmacology Biochemistry and Behavior.

[9]  Y. Kan,et al.  Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  P. Blissitt.  Sleep, Memory, and Learning , 2001, The Journal of neuroscience nursing : journal of the American Association of Neuroscience Nurses.

[11]  Kathleen K. Ohlmann,et al.  The costs of short sleep. , 2009, AAOHN journal : official journal of the American Association of Occupational Health Nurses.

[12]  K. Alzoubi,et al.  Post-learning REM sleep deprivation impairs long-term memory: Reversal by acute nicotine treatment , 2011, Neuroscience Letters.

[13]  Xinmin Liu,et al.  Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method , 2016, Behavioural Brain Research.

[14]  J. A. C. EMPSON,et al.  Rapid Eye Movements and Remembering , 1970, Nature.

[15]  D. Butterfield,et al.  Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide. , 2001, Trends in molecular medicine.

[16]  Lei Zhang,et al.  Melatonin ameliorates cognitive impairment induced by sleep deprivation in rats: Role of oxidative stress, BDNF and CaMKII , 2013, Behavioural Brain Research.

[17]  C. Sung,et al.  Long-term administration of ginsenoside Rh1 enhances learning and memory by promoting cell survival in the mouse hippocampus. , 2014, International journal of molecular medicine.

[18]  Madhur Gupta,et al.  Neuroprotective role of melatonin in oxidative stress vulnerable brain. , 2003, Indian journal of physiology and pharmacology.

[19]  G. Bertini,et al.  Experimental sleep deprivation as a tool to test memory deficits in rodents , 2013, Front. Syst. Neurosci..

[20]  A. Ennaceur,et al.  A new one-trial test for neurobiological studies of memory in rats. III. Spatial vs. non-spatial working memory , 1992, Behavioural Brain Research.

[21]  L. Jia,et al.  Current evaluation of the millennium phytomedicine- ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. , 2009, Current medicinal chemistry.

[22]  F. Jiang,et al.  [Effects of chronic partial sleep deprivation on growth and learning/memory in young rats]. , 2009, Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics.

[23]  J. Siegel,et al.  Sleep deprivation decreases superoxide dismutase activity in rat hippocampus and brainstem , 2002, Neuroreport.

[24]  K. Alzoubi,et al.  The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: The role of oxidative stress , 2012, Behavioural Brain Research.

[25]  Carlyle Smith,et al.  Paradoxical sleep deprivation applied two days after end of training retards learning , 1988, Physiology & Behavior.

[26]  N. Chen,et al.  Improvement of memory in mice and increase of hippocampal excitability in rats by ginsenoside Rg1's metabolites ginsenoside Rh1 and protopanaxatriol. , 2009, Journal of pharmacological sciences.

[27]  K. Alzoubi,et al.  Tempol prevents chronic sleep-deprivation induced memory impairment , 2016, Brain Research Bulletin.

[28]  I. Cho.  Effects of Panax ginseng in Neurodegenerative Diseases , 2012, Journal of ginseng research.

[29]  C. Czeisler.  Medical and genetic differences in the adverse impact of sleep loss on performance: ethical considerations for the medical profession. , 2009, Transactions of the American Clinical and Climatological Association.

[30]  Jeffrey C Magee,et al.  Sleep deprivation‐induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus , 2006, The Journal of physiology.

[31]  I. Alhaider,et al.  Caffeine prevents sleep loss‐induced deficits in long‐term potentiation and related signaling molecules in the dentate gyrus , 2010, The European journal of neuroscience.

[32]  E. Reimund.  The free radical flux theory of sleep. , 1994, Medical hypotheses.

[33]  E. Williamson,et al.  Effects and mechanisms of ginseng and ginsenosides on cognition. , 2014, Nutrition reviews.

[34]  F. Chauveau,et al.  Modafinil restores memory performance and neural activity impaired by sleep deprivation in mice , 2007, Pharmacology Biochemistry and Behavior.

[35]  S. Okuda,et al.  Characteristics of object location memory in mice: Behavioral and pharmacological studies , 2007, Physiology & Behavior.

[36]  A. Steinmetz,et al.  Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine‐induced learning and memory impairment in mice , 2010, Phytotherapy research : PTR.

[37]  K. Baskerville,et al.  Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents , 2001, Neuroscience.

[38]  J. Horne,et al.  Sleep Loss and Temporal Memory , 2000, The Quarterly journal of experimental psychology. A, Human experimental psychology.

[39]  Salim S. Al-Rejaie,et al.  Acute nicotine treatment prevents rem sleep deprivation‐induced learning and memory impairment in rat , 2010, Hippocampus.

[40]  K. Alzoubi,et al.  Vitamin E prevents high-fat high-carbohydrates diet-induced memory impairment: The role of oxidative stress , 2013, Physiology & Behavior.

[41]  S. Tufik,et al.  Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice , 2004, Neuropharmacology.

[42]  D. Sharma,et al.  Effect of paradoxical sleep deprivation on oxidative stress parameters in brain regions of adult and old rats , 2008, Biogerontology.

[43]  K. Rosenblum,et al.  Lateral ventricle injection of the protein synthesis inhibitor anisomycin impairs long-term memory in a spatial memory task , 1998, Brain Research.