title: Neuroprotective effects of Danggui-Jakyak-San on rat stroke model through antioxidant/antiapoptotic pathway.
abstract: BACKGROUND
  Dangui-Jakyak-San (DJ) is a traditional Korean medicinal polyherb, prescribed typically in patients with insufficient blood supply in Eastern Asia. The DJ also has been reported to have neuroprotective effects in vitro and in vivo studies.
  
  
  OBJECTIVE
  The therapeutic potential of DJ was examined in stroke rat model, in comparison with donepezil, a reversible acetylcholinesterase inhibitor.
  
  
  METHODS
  Ischemic stroke rat model was induced by surgery of permanent occlusion of middle cerebral artery (pMCAO). The model was orally administered with distilled water (pMCAO control), donepezil at 10mg/kg (Donepezil) and DJ at 200, 100 and 50mg/kg (DJ 200, DJ 100 and DJ 50, respectively). Sham had the same surgery excepting for the pMCAO, and it was administered with distilled water (sham control).
  
  
  RESULTS
  After the administration for 28 days, the groups of DJ exhibited dose-dependent reduction in infarct/defect volumes with improvement in sensorimotor and cognitive motor function, comparing to pMCAO control. The DJ treatments seemed to enhance antiapoptotic and antioxidant effects; increases in antiapoptotic expressions (STAT3 and Pim-1) and decreases in lipid peroxidation (MDA) together with increases in contents of endogenous antioxidant (GSH) and activities of antioxidant enzymes (catalase and SOD). The histopathological analyses revealed significant reduction in neuronal apoptosis (caspase-3 and PARP) and neuronal degradation with atrophy and degeneration, in the DJ treatments. Furthermore, the oxidative stresses (nitrotyrosine as an iNOS factor and 4-HNE as a marker of lipid peroxidation) were observed mild. Although the similar neuroprotective effects were observed, the body weight loss was scarcely alleviated in Donepezil comparing to pMCAO control.
  
  
  CONCLUSIONS
  These suggest that DJ ameliorate the neurological dysfunction of cerebral ischemia through augmentation of antioxidant defense system and up-regulation of STAT3 and Pim-1.
authors.affiliation: Department of Oriental Neuropsychiatry, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Oriental Neuropsychiatry, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
authors.forename: Dae-Kyoo
authors.initials: DK
authors.lastname: Chung
authors.affiliation: Department of Preventive Medicine, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea. Electronic address: dvmsong@hotmail.com.
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Song
authors.affiliation: Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea. Electronic address: gucci200@hanmail.net.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007189:Indans / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D004365:Drugs, Chinese Herbal; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C531150:danggui-shaoyao-san; D000077265:Donepezil; D011065:Poly(ADP-ribose) Polymerases; C496637:Pim1 protein, rat; D051573:Proto-Oncogene Proteins c-pim-1; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: 2,3,5-triphenyltetrazolium chloride (PubChem CID: 9283); 2-nitrobenzoic acid (PubChem CID: 6254); Antioxidant; Apoptosis; Danggui-Jakyak-San; Donepezil hydrochloride (PubChem CID: 5741); Enrofloxacin (PubChem CID: 71188); Glutathione (PubChem CID: 124886); Ischemic stroke; Isoflurane (PubChem CID: 3763); Malondialdehyde (PubChem CID: 10964); Polyherb; Thiobarbituric acid (PubChem CID: 2723628); Trichloroacetic acid (PubChem CID: 6421); Tris–HCl (PubChem CID: 93573)