title: Gastrodin improves cognitive dysfunction and decreases oxidative stress in vascular dementia rats induced by chronic ischemia.
abstract: OBJECTIVE
  To study the potential protective effects of gastrodin on reducing tissue oxidative stress and attenuating cognitive deficits in vascular dementia induced by cerebral chronic hyperfusion. To explore the detailed molecular mechanisms.
  
  
  METHODS
  6 to 8 week old male Wistar rats were adopted as experimental animals. Animals were divided into the following groups: Group 1 (sham group with no occlusion), Group 2 (control group with 2VO procedure), Group 3 (sham group with gastrodin administration), Group 4 (2VO group with gastrodin administration). Morris water maze (MWM) test was adopted to test the learning and memory function of rats within different groups. MDA, glutathione peroxidase and total thiol assessment was done to reflect the oxidative stress in the brain tissue. Cell counting kit-8 (CCK8) and flow cytometry (FCM) were performed to examine the cell viability and apoptosis rate of SH-SY5Y cells induced by hydrogen peroxide and rescued by gastrodin treatments. Reactive oxygen species (ROS) generation was determined by the 2', 7'-dichlorofluorescein diacetate (DCFH-DA) assay. qPCR and Western blot (WB) were adopted to detect the molecular mechanisms related to the anti-apoptosis and ROS scavenging effects of gastrodin.
  
  
  RESULTS
  Our results indicated an obvious protective effect of gastrodin on vascular dementia induced brain ischemia. Administration of gastrodin could improve the impaired learning and memory function induced by 2VO procedure in rats. The levels of MDA were partially decreased by the administration of gastrodin. The levels of glutathione peroxidase and total thiol were partially restored by the administration of gastrodin. Cell viability was improved by gastrodin in a dose-dependent pattern on SH-SY5Y cells induced by hydrogen peroxide (P < 0.05). Cell apoptosis rate was reduced by gastrodin in a dose-dependent pattern on SH-SY5Y cells induced by hydrogen peroxide (P < 0.05). Gastrodin could scavenge ROS generation induced by pre-treatment of hydrogen peroxide. Both qPCR and WB results showed significant enhancements on the expression levels of NFE2L2, ADH7, GPX2 and GPX3 (P < 0.05).
  
  
  CONCLUSIONS
  Gastrodin administration is protective on the learning and memory functions that might be affected by vascular dementia induced oxidative stress due to brain ischemia. On the molecular level, NFE2L2, ADH7, GPX2 and GPX3 were up regulated by gastrodin.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University Jinzhou 121000, Liaoning Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University Jinzhou 121000, Liaoning Province, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001592:Benzyl Alcohols / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications* / Q000503:physiopathology; D045744:Cell Line, Tumor; D002560:Cerebrovascular Circulation; D002908:Chronic Disease; D003071:Cognition / Q000187:drug effects*; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005960:Glucosides / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D001592:Benzyl Alcohols; D005960:Glucosides; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; C045345:gastrodin; C526911:ADH7 protein, human; D000426:Alcohol Dehydrogenase; C117436:GPX2 protein, human; C486484:GPX3 protein, human; D005979:Glutathione Peroxidase
keywords: NFE2L2; Vascular dementia; cognitive dysfunction; gastrodin; oxidative stress
references.citation: Proc Soc Exp Biol Med. 1999 Dec;222(3):236-45
references.pmid: 10601882
references.citation: Pharmacol Rep. 2013;65(2):288-304
references.pmid: 23744414
references.citation: Oxid Med Cell Longev. 2013;2013:297357
references.pmid: 23691263
references.citation: Brain Res. 1996 Aug 5;729(1):55-65
references.pmid: 8874876
references.citation: Acta Neurol Belg. 2009 Sep;109(3):171-80
references.pmid: 19902810
references.citation: Oxid Med Cell Longev. 2013;2013:963520
references.pmid: 24381719
references.citation: Life Sci. 2014 Oct 2;114(2):77-85
references.pmid: 25132361
references.citation: Int J Hypertens. 2012;2012:169649
references.pmid: 23304450
references.citation: Mol Cell Biochem. 2012 Jan;359(1-2):9-16
references.pmid: 21833534
references.citation: Brain Res. 1988 Jun 7;451(1-2):205-12
references.pmid: 2472189
references.citation: Cell Mol Life Sci. 2012 Jul;69(14):2387-407
references.pmid: 22643836
references.citation: Eur J Pharmacol. 2007 Oct 1;571(2-3):120-8
references.pmid: 17597609
references.citation: Biol Trace Elem Res. 2010 Dec;138(1-3):238-49
references.pmid: 20177816
references.citation: Cell Mol Life Sci. 2012 Jul;69(14):2345-63
references.pmid: 22618244
references.citation: Bone. 2015 Apr;73:132-44
references.pmid: 25554600
references.citation: Biomed Res Int. 2013;2013:484613
references.pmid: 24455696
references.citation: Prog Neurobiol. 2013 Jan;100:30-47
references.pmid: 23025925
references.citation: Neuropharmacology. 2014 Apr;79:298-306
references.pmid: 24262633
references.citation: Prog Neurobiol. 2013 Jul-Aug;106-107:33-54
references.pmid: 23827971
references.citation: J Alzheimers Dis. 2011;26 Suppl 3:123-33
references.pmid: 21971457
references.citation: Neural Plast. 2014;2014:320937
references.pmid: 25485157
references.citation: Biull Eksp Biol Med. 1988 Apr;105(4):394-7
references.pmid: 3359013
references.citation: Mol Med Rep. 2013 Aug;8(2):585-90
references.pmid: 23783886
references.citation: Pflugers Arch. 2013 Jan;465(1):133-51
references.pmid: 22535332
references.citation: Circ Res. 2012 Apr 27;110(9):1238-51
references.pmid: 22539757
references.citation: Mol Neurobiol. 2013 Feb;47(1):9-23
references.pmid: 23011809
references.citation: Acta Biochim Biophys Sin (Shanghai). 2012 Nov;44(11):897-901
references.pmid: 22935512
references.citation: Neurochem Res. 2011 Oct;36(10):1840-9
references.pmid: 21603936
references.citation: Brain Res. 1995 Mar 6;673(2):290-6
references.pmid: 7606443
references.citation: Psychopharmacol Bull. 1998;34(3):391-7
references.pmid: 9803773
references.citation: J Stroke Cerebrovasc Dis. 2000 Nov;9(6 Pt 2):2-8
references.pmid: 17895213
references.citation: Brain Res Rev. 2007 Apr;54(1):162-80
references.pmid: 17296232
references.citation: Neurochem Int. 2012 Jan;60(2):208-12
references.pmid: 22122807
references.citation: Int J Mol Sci. 2013;14(12):24438-75
references.pmid: 24351827
references.citation: Eur J Pharmacol. 2014 Jun 15;733:62-7
references.pmid: 24726557