title: Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats.
abstract: BACKGROUND
  Withania somnifera (WS) root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer and anti-stress agent.
  
  
  OBJECTIVE
  To evaluate the neuroprotective and prophylactic potential of WS root extract in ameliorating hypobaric hypoxia (HH) induced memory impairment and to explore the underlying molecular mechanism.
  
  
  METHODS
  WS root extract was administered to male Sprague Dawley rats during a period of 21 days pre-exposure and 07 days exposure to a simulated altitude of 25,000 ft. Spatial memory was assessed by Morris Water Maze. Neurodegeneration, corticosterone, acetylcholine (Ach) levels, acetylcholine esterase (AchE) activity, oxidative stress markers and nitric oxide (NO) concentration were assessed in the hippocampus. Synaptic and apoptotic markers were also investigated by immunoblotting. To study the role of NO in regulating corticosterone mediated signaling, the neuronal nitric oxide synthase (n-NOS) inhibitor, L-Nitro-arginine methyl ester (L-Name) and NO agonist sodium nitroprusside (SNP) were administered from 3rd to 7th day of hypoxic exposure.
  
  
  RESULTS
  Administration of WS root extract prevented HH induced memory impairment and neurodegeneration along with decreased NO, corticosterone, oxidative stress and AchE activity in hippocampal region. Inhibition of NO synthesis by administration of L-Name reduced corticosterone levels in hippocampus during hypoxic exposure while co-administration of corticosterone increased neurodegeneration. Administration of sodium nitroprusside (SNP) along with WS root extract supplementation during hypoxic exposure increased corticosterone levels and increased the number of pyknotic cells.
  
  
  CONCLUSIONS
  WS root extract ameliorated HH induced memory impairment and neurodegeneration in hippocampus through NO mediated modulation of corticosterone levels.
authors.affiliation: Defence Institute of Physiology and Allied Sciences, DRDO, At/Po: Timarpur, Lucknow Road, Delhi-110054, India.
authors.forename: Iswar
authors.initials: I
authors.lastname: Baitharu
authors.forename: Vishal
authors.initials: V
authors.lastname: Jain
authors.forename: Satya Narayan
authors.initials: SN
authors.lastname: Deep
authors.forename: Kalpana Barhwal
authors.initials: KB
authors.lastname: Hota
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Hota
authors.forename: Dipti
authors.initials: D
authors.lastname: Prasad
authors.forename: Govindasamy
authors.initials: G
authors.lastname: Ilavazhagan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D000860:Hypoxia / Q000150:complications; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D032341:Withania
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020746:Calcium Channels, L-Type; D019006:Neural Cell Adhesion Molecules; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016708:Synaptophysin; C569016:Syp protein, rat; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D005978:Glutathione; D000109:Acetylcholine; D003345:Corticosterone