title: Activating mitochondrial function and haemoglobin expression with EH-201, an inducer of erythropoietin in neuronal cells, reverses memory impairment.
abstract: OBJECTIVE
  Memory impairment can be progressive in neurodegenerative diseases, and physiological ageing or brain injury, mitochondrial dysfunction and oxidative stress are critical components of these issues. An early clinical study has demonstrated cognitive improvement during erythropoietin treatment in patients with chronic renal failure. As erythropoietin cannot freely cross the blood-brain barrier, we tested EH-201 (2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, also known as TSG), a low MW inducer of erythropoietin, for its therapeutic effects on memory impairment in models of neurodegenerative diseases, physiological ageing or brain injury.
  
  
  METHODS
  The effects of EH-201 were investigated in astrocytes and PC12 neuronal-like cells. In vivo, we used sleep-deprived (SD) mice as a stress model, amyloid-β (Aβ)-injected mice as a physiological ageing model and kainic acid (KA)-injected mice as a brain damage model to assess the therapeutic effects of EH-201.
  
  
  RESULTS
  EH-201 induced expression of erythropoietin, PPAR-γ coactivator 1α (PGC-1α) and haemoglobin in astrocytes and PC12 neuronal-like cells. In vivo, EH-201 treatment restored memory impairment, as assessed by the passive avoidance test, in SD, Aβ and KA mouse models. In the hippocampus of mice given EH-201 in their diet, levels of erythropoietin, PGC-1α and haemoglobin were increased
  
  
  CONCLUSIONS
  The induction of endogenous erythropoietin in neuronal cells by inducers such as EH-201 might be a therapeutic strategy for memory impairment in neurodegenerative disease, physiological ageing or traumatic brain injury.
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.|Research Center for Drug Discovery, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Lin-Yea
authors.initials: LY
authors.lastname: Horng
authors.affiliation: Research Center for Drug Discovery, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pei-Lun
authors.initials: PL
authors.lastname: Hsu
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Chen
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wang-Zou
authors.initials: WZ
authors.lastname: Tseng
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kai-Tin
authors.initials: KT
authors.lastname: Hsu
authors.affiliation: Research Center for Drug Discovery, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Wu
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.|Research Center for Drug Discovery, National Yang-Ming University, Taipei, Taiwan.|Research Center for Natural Products and Drug Development, Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Rong-Tsun
authors.initials: RT
authors.lastname: Wu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D006861:Hydrogen Peroxide; D007608:Kainic Acid; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016716:PC12 Cells; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005960:Glucosides; D006454:Hemoglobins; D018696:Neuroprotective Agents; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014157:Transcription Factors; D004921:Erythropoietin; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D006861:Hydrogen Peroxide; D013385:Succinate Dehydrogenase; D007608:Kainic Acid