3,5,6,7,8,3′,4′-Heptamethoxyflavone, a Citrus Flavonoid, Ameliorates Corticosterone-Induced Depression-like Behavior and Restores Brain-Derived Neurotrophic Factor Expression, Neurogenesis, and Neuroplasticity in the Hippocampus

被引：56

作者：

Sawamoto, Atsushi ^{[1
]}

Okuyama, Satoshi ^{[1
]}

Yamamoto, Kana ^{[1
]}

Amakura, Yoshiaki ^{[2
]}

Yoshimura, Morio ^{[2
]}

Nakajima, Mitsunari ^{[1
]}

Furukawa, Yoshiko ^{[1
]}

机构：

[1] Matsuyama Univ, Coll Pharmaceut Sci, Dept Pharmaceut Pharmacol, 4-2 Bunkyo Cho, Matsuyama, Ehime 7908578, Japan

[2] Matsuyama Univ, Coll Pharmaceut Sci, Dept Pharmacognosy, 4-2 Bunkyo Cho, Matsuyama, Ehime 7908578, Japan

来源：

MOLECULES | 2016年 / 21卷 / 04期

关键词：

heptamethoxyflavone; depression; corticosterone; hippocampus; brain-derived neurotrophic factor; neurogenesis; ANTAGONIST MIFEPRISTONE NORMALIZES; MAP KINASE; MODEL; ANTIDEPRESSANTS; FLUOXETINE; PLASTICITY; STRESS; MOUSE; IMPAIRMENT; REDUCTION;

D O I：

10.3390/molecules21040541

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We previously reported that the citrus flavonoid 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) increased the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of a transient global ischemia mouse model. Since the BDNF hypothesis of depression postulates that a reduction in BDNF is directly involved in the pathophysiology of depression, we evaluated the anti-depressive effects of HMF in mice with subcutaneously administered corticosterone at a dose of 20 mg/kg/day for 25 days. We demonstrated that the HMF treatment ameliorated (1) corticosterone-induced body weight loss, (2) corticosterone-induced depression-like behavior, and (3) corticosterone-induced reductions in BDNF production in the hippocampus. We also showed that the HMF treatment restored (4) corticosterone-induced reductions in neurogenesis in the dentate gyrus subgranular zone and (5) corticosterone-induced reductions in the expression levels of phosphorylated calcium-calmodulin-dependent protein kinase II and extracellular signal-regulated kinase1/2. These results suggest that HMF exerts its effects as an anti-depressant drug by inducing the expression of BDNF.

引用

页数：13