PMID- 29023414
OWN - NLM
STAT- MEDLINE
DCOM- 20180530
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 10
DP  - 2017 Oct 12
TI  - 3,5,6,7,8,3',4'-Heptamethoxyflavone Ameliorates Depressive-Like Behavior and 
      Hippocampal Neurochemical Changes in Chronic Unpredictable Mild Stressed Mice by 
      Regulating the Brain-Derived Neurotrophic Factor: Requirement for ERK Activation.
LID - 10.3390/ijms18102133 [doi]
LID - 2133
AB  - We previously reported that the subcutaneous administration of 
      3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), a citrus polymethoxyflavone, 
      attenuated depressive-like behavior and increased the expression of brain-derived 
      neurotrophic factor (BDNF) in the hippocampus of a corticosterone-induced 
      depression-like mouse model. We herein demonstrated that (1) HMF was detectable 
      in the brain 10 and 30 min after its oral administration, (2) orally administered 
      HMF improved chronic unpredictable mild stress (CUMS)-induced pathological 
      conditions, including body weight loss and depressive-like behavior, and 
      CUMS-induced neurochemical changes, such as reduction in BDNF expression, 
      decrease in neurogenesis, and decreased level of phosphorylated 
      calcium-calmodulin-dependent protein kinase II in the hippocampus, and (3) these 
      effects of HMF were inhibited by the pre-administration of U0126, a 
      mitogen-activated protein (MAP) kinase inhibitor. These results suggest that 
      orally administered HMF is beneficial for the upregulation of BDNF in the 
      hippocampus via the extracellular signal-regulated kinase1/2 (ERK1/2)/MAP system, 
      which may account for its antidepression effects.
FAU - Sawamoto, Atsushi
AU  - Sawamoto A
AD  - Department of Pharmaceutical Pharmacology, Graduate school of Clinical Pharmacy, 
      Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 
      46140018@g.matsuyama-u.ac.jp.
FAU - Okuyama, Satoshi
AU  - Okuyama S
AD  - Department of Pharmaceutical Pharmacology, Graduate school of Clinical Pharmacy, 
      Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 
      sokuyama@g.matsuyama-u.ac.jp.
FAU - Amakura, Yoshiaki
AU  - Amakura Y
AD  - Department of Pharmacognosy, Graduate school of Clinical Pharmacy, Matsuyama 
      University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 
      amakura@g.matsuyama-u.ac.jp.
FAU - Yoshimura, Morio
AU  - Yoshimura M
AD  - Department of Pharmacognosy, Graduate school of Clinical Pharmacy, Matsuyama 
      University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 
      myoshimu@g.matsuyama-u.ac.jp.
FAU - Yamada, Takashi
AU  - Yamada T
AD  - Department of Food and Nutritional Sciences, College of Bioscience and 
      Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, 
      Japan. yamadat@nagoya-ku.ac.jp.
FAU - Yokogoshi, Hidehiko
AU  - Yokogoshi H
AD  - Department of Food and Nutritional Sciences, College of Bioscience and 
      Biotechnology, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, 
      Japan. yokogoshi@isc.chubu.ac.jp.
FAU - Nakajima, Mitsunari
AU  - Nakajima M
AD  - Department of Pharmaceutical Pharmacology, Graduate school of Clinical Pharmacy, 
      Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 
      mnakajim@g.matsuyama-u.ac.jp.
FAU - Furukawa, Yoshiko
AU  - Furukawa Y
AUID- ORCID: 0000-0003-1233-3526
AD  - Department of Pharmaceutical Pharmacology, Graduate school of Clinical Pharmacy, 
      Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. 
      furukawa@g.matsuyama-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20171012
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Flavonoids)
RN  - 0 (Glucocorticoids)
RN  - 1178-24-1 (3,3',4',5,6,7,8-heptamethoxyflavone)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - *Behavior, Animal
MH  - Biomarkers
MH  - Brain/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Depression/drug therapy/etiology/*metabolism/*psychology
MH  - Disease Models, Animal
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Flavonoids/administration & dosage/pharmacokinetics/*pharmacology
MH  - Gene Expression
MH  - Glucocorticoids/blood
MH  - Hippocampus/*drug effects/*metabolism/physiopathology
MH  - Male
MH  - Mice
MH  - Neurogenesis
MH  - Phosphorylation
MH  - *Stress, Psychological
MH  - Tissue Distribution
PMC - PMC5666815
OTO - NOTNLM
OT  - 3,5,6,7,8,3',4'-heptamethoxyflavone
OT  - HMF
OT  - astrocyte
OT  - brain-derived neurotrophic factor
OT  - depression
OT  - neurogenesis
OT  - neuroplasticity
COIS- The authors declare no conflict of interest.
EDAT- 2017/10/13 06:00
MHDA- 2018/05/31 06:00
PMCR- 2017/10/01
CRDT- 2017/10/13 06:00
PHST- 2017/08/29 00:00 [received]
PHST- 2017/10/06 00:00 [revised]
PHST- 2017/10/09 00:00 [accepted]
PHST- 2017/10/13 06:00 [entrez]
PHST- 2017/10/13 06:00 [pubmed]
PHST- 2018/05/31 06:00 [medline]
PHST- 2017/10/01 00:00 [pmc-release]
AID - ijms18102133 [pii]
AID - ijms-18-02133 [pii]
AID - 10.3390/ijms18102133 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Oct 12;18(10):2133. doi: 10.3390/ijms18102133.