PMID- 26177968
OWN - NLM
STAT- MEDLINE
DCOM- 20160706
LR  - 20181113
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 172
IP  - 19
DP  - 2015 Oct
TI  - Activating mitochondrial function and haemoglobin expression with EH-201, an 
      inducer of erythropoietin in neuronal cells, reverses memory impairment.
PG  - 4741-56
LID - 10.1111/bph.13248 [doi]
AB  - BACKGROUND AND PURPOSE: 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-beta-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. 
      EXPERIMENTAL APPROACH: 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-beta (Abeta)-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. KEY RESULTS: EH-201 induced expression of erythropoietin, PPAR-gamma 
      coactivator 1alpha (PGC-1alpha) 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, Abeta and KA mouse models. In the hippocampus of mice 
      given EH-201 in their diet, levels of erythropoietin, PGC-1alpha and haemoglobin were 
      increased CONCLUSIONS AND IMPLICATIONS: 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.
CI  - (c) 2015 The Authors. British Journal of Pharmacology published by John Wiley & 
      Sons Ltd on behalf of The British Pharmacological Society.
FAU - Horng, Lin-Yea
AU  - Horng LY
AD  - Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, 
      Taiwan.
AD  - Research Center for Drug Discovery, National Yang-Ming University, Taipei, 
      Taiwan.
FAU - Hsu, Pei-Lun
AU  - Hsu PL
AD  - Research Center for Drug Discovery, National Yang-Ming University, Taipei, 
      Taiwan.
FAU - Chen, Li-Wen
AU  - Chen LW
AD  - Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, 
      Taiwan.
FAU - Tseng, Wang-Zou
AU  - Tseng WZ
AD  - Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, 
      Taiwan.
FAU - Hsu, Kai-Tin
AU  - Hsu KT
AD  - Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, 
      Taiwan.
FAU - Wu, Chia-Ling
AU  - Wu CL
AD  - Research Center for Drug Discovery, National Yang-Ming University, Taipei, 
      Taiwan.
FAU - Wu, Rong-Tsun
AU  - Wu RT
AD  - Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, 
      Taiwan.
AD  - Research Center for Drug Discovery, National Yang-Ming University, Taipei, 
      Taiwan.
AD  - Research Center for Natural Products and Drug Development, Institute of Natural 
      Products, Kaohsiung Medical University, Kaohsiung, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150810
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Glucosides)
RN  - 0 (Hemoglobins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Ppargc1a protein, rat)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Stilbenes)
RN  - 0 (Transcription Factors)
RN  - 11096-26-7 (Erythropoietin)
RN  - 133186-49-9 (2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Erythropoietin/*metabolism
MH  - Female
MH  - Glucosides/pharmacology/*therapeutic use
MH  - Hemoglobins/metabolism
MH  - Hydrogen Peroxide
MH  - Kainic Acid
MH  - Male
MH  - Memory Disorders/*drug therapy/metabolism
MH  - Mice, Inbred C57BL
MH  - Mitochondria/drug effects/metabolism
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - PC12 Cells
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Stilbenes/pharmacology/*therapeutic use
MH  - Succinate Dehydrogenase/metabolism
MH  - Transcription Factors/genetics/metabolism
PMC - PMC4594276
EDAT- 2015/07/17 06:00
MHDA- 2016/07/07 06:00
PMCR- 2016/10/01
CRDT- 2015/07/17 06:00
PHST- 2015/02/28 00:00 [received]
PHST- 2015/06/29 00:00 [revised]
PHST- 2015/07/02 00:00 [accepted]
PHST- 2015/07/17 06:00 [entrez]
PHST- 2015/07/17 06:00 [pubmed]
PHST- 2016/07/07 06:00 [medline]
PHST- 2016/10/01 00:00 [pmc-release]
AID - 10.1111/bph.13248 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2015 Oct;172(19):4741-56. doi: 10.1111/bph.13248. Epub 2015 Aug 
      10.