title: Neuroprotective effect of oral S/B remedy (Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd) on iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain.
abstract: OBJECTIVE
  S/B remedy prepared from Scutellaria baicalensis Georgi and Bupleurum scorzonerifolfium Willd, two herbals of Xiao-Tsai-Hu-Tang or Sho-Saiko-To (TJ-9), contains active flavonoids. In this study, the protective effect of S/B remedy on iron-induced neurodegeneration was investigated in the nigrostriatal dopaminergic system of rat brain.
  
  
  METHODS
  The antioxidative activity of S/B remedy was studied using brain homogenates incubated with ferrous citrate (iron, 1M), S/B remedy, Trolox and melatonin. Furthermore, a Parkinsonian animal model by an intranigral infusion of iron in the anesthetized rats was employed to investigate the protective effect of S/B remedy in the nigrostriatal dopaminergic system.
  
  
  RESULTS
  Our in vitro studies showed that S/B remedy was more potent than melatonin and equal to trolox in inhibiting iron-induced lipid peroxidation of brain homogenates. Our in vivo studies found that oral administration of S/B remedy dose-dependently attenuated iron-elevated lipid peroxidation in the infused substantia nigra (SN) and iron-depleted dopamine levels in the ipsilateral striatum. Furthermore, iron-induced reductions in glutathione (GSH) content and increases in GSSG (oxidized GSH)/GSH ratio in the infused SN were inhibited in S/B remedy-treated rats. Systemic S/B remedy attenuated the iron-induced increases in heme-oxygenase-1 levels and α-synuclein aggregation in the infused SN. Moreover, S/B remedy reduced iron-induced apoptosis via attenuating mitochondrial and endoplasmic reticulum stress. In addition, S/B remedy was anti-inflammatory as indicated by the attenuation of iron-induced elevations in inducible nitric oxide synthase and cyclo-oxygenase II levels as well as glial fibrillary acidic protein (a biological marker of astrocytes) and ED-1 (a protein indicative of activated microglia) levels in the infused SN of S/B remedy-treated rats.
  
  
  CONCLUSIONS
  These findings suggest that oral administration of S/B remedy is protective against iron-induced neurodegeneration in the nigrostriatal dopaminergic system of rat brain. Therefore, S/B remedy may be therapeutically useful for the treatment of CNS neurodegenerative diseases.
authors.affiliation: Department of Pharmacology, School of Medicine, National Yang-Ming University, Taiwan, ROC. myalin@vghtpe.gov.tw
authors.forename: Anya M Y
authors.initials: AM
authors.lastname: Lin
authors.forename: Y H
authors.initials: YH
authors.lastname: Ping
authors.forename: G F
authors.initials: GF
authors.lastname: Chang
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: J H
authors.initials: JH
authors.lastname: Chiu
authors.forename: C D
authors.initials: CD
authors.lastname: Kuo
authors.forename: C W
authors.initials: CW
authors.lastname: Chi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D029972:Bupleurum; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D007501:Iron / Q000633:toxicity*; D015227:Lipid Peroxidation; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D031364:Scutellaria baicalensis / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; C051274:Bupleurum root extract; D018696:Neuroprotective Agents; D010936:Plant Extracts; D007501:Iron; D004298:Dopamine