PMID- 29510125
OWN - NLM
STAT- MEDLINE
DCOM- 20180910
LR  - 20181202
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 826
DP  - 2018 May 5
TI  - 6,7,4'-Trihydroxyisoflavone, a major metabolite of daidzein, improves learning 
      and memory via the cholinergic system and the p-CREB/BDNF signaling pathway in 
      mice.
PG  - 140-147
LID - S0014-2999(18)30131-6 [pii]
LID - 10.1016/j.ejphar.2018.02.048 [doi]
AB  - Daidzein is one of the major isoflavfones found in soy food and plants. Following 
      ingestion, daidzein is readily converted to hydroxylated metabolites in the human 
      body. 6,7,4'-Trihydroxyisoflavone (THIF), one of the metabolites of daidzein, has 
      several pharmacological activities, including anti-cancer and anti-obesity 
      properties. However, no reports exist on the effects of 6,7,4'-THIF for cognitive 
      function in mice. The present study aimed to investigate the effects of 
      6,7,4'-THIF against scopolamine-induced learning and memory impairments using the 
      Y-maze and passive avoidance test. A single administration of 6,7,4'-THIF 
      significantly improved scopolamine-induced cognitive dysfunction in these in vivo 
      tests. Moreover, treatment with 6,7,4'-THIF alone enhanced learning and memory 
      performance in the same behavioral tests. Molecular studies showed that 
      6,7,4'-THIF significantly inhibited acetylcholinesterase and thiobarbituric acid 
      reactive substance (TBARS) activities in the hippocampus of scopolamine-induced 
      mice. In addition, immunohistochemistry and Western blot results revealed that 
      6,7,4'-THIF significantly increased brain-derived neurotrophic factor (BDNF) and 
      phosphor cAMP response element binding (CREB) in the hippocampus of mice. Taken 
      together, these findings suggest that 6,7,4'-THIF improves cognitive dysfunction 
      induced by scopolamine and enhances learning and memory by activation of the 
      cholinergic system and the p-CREB/BDNF signaling pathway in mice.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Ko, Yong-Hyun
AU  - Ko YH
AD  - Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 
      16419, Republic of Korea.
FAU - Kim, Sun Yeou
AU  - Kim SY
AD  - College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea.
FAU - Lee, Seok-Yong
AU  - Lee SY
AD  - Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 
      16419, Republic of Korea.
FAU - Jang, Choon-Gon
AU  - Jang CG
AD  - Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 
      16419, Republic of Korea. Electronic address: jang@skku.edu.
LA  - eng
PT  - Journal Article
DEP - 20180303
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (6,7,4'-trihydroxyisoflavone)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cholinergic Agents)
RN  - 0 (Creb1 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Isoflavones)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 6287WC5J2L (daidzein)
RN  - DL48G20X8X (Scopolamine)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase/*metabolism
MH  - Animals
MH  - Avoidance Learning/drug effects
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cholinergic Agents
MH  - Cognition/drug effects
MH  - Cognitive Dysfunction/chemically induced/*drug therapy/pathology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Disease Models, Animal
MH  - Hippocampus/drug effects/metabolism/pathology
MH  - Humans
MH  - Isoflavones/metabolism/*pharmacology/therapeutic use
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Maze Learning
MH  - Memory Disorders/chemically induced/*drug therapy/pathology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Phosphorylation
MH  - Scopolamine/toxicity
MH  - Signal Transduction/*drug effects
MH  - Thiobarbituric Acid Reactive Substances/metabolism
OTO - NOTNLM
OT  - 6,7,4'-Trihydroxyisoflavone
OT  - Alzheimer's disease
OT  - Brain-derived neurotrophic factor
OT  - Cognition
OT  - cAMP response element binding
EDAT- 2018/03/07 06:00
MHDA- 2018/09/11 06:00
CRDT- 2018/03/07 06:00
PHST- 2017/11/03 00:00 [received]
PHST- 2018/02/09 00:00 [revised]
PHST- 2018/02/28 00:00 [accepted]
PHST- 2018/03/07 06:00 [pubmed]
PHST- 2018/09/11 06:00 [medline]
PHST- 2018/03/07 06:00 [entrez]
AID - S0014-2999(18)30131-6 [pii]
AID - 10.1016/j.ejphar.2018.02.048 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2018 May 5;826:140-147. doi: 10.1016/j.ejphar.2018.02.048. Epub 
      2018 Mar 3.