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Molecules 2016, 21(4), 541; doi:10.3390/molecules21040541

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

1
Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan
2
Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Luigia Trabace
Received: 2 March 2016 / Revised: 20 April 2016 / Accepted: 21 April 2016 / Published: 23 April 2016
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Abstract

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. View Full-Text
Keywords: heptamethoxyflavone; depression; corticosterone; hippocampus; brain-derived neurotrophic factor; neurogenesis heptamethoxyflavone; depression; corticosterone; hippocampus; brain-derived neurotrophic factor; neurogenesis
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Sawamoto, A.; Okuyama, S.; Yamamoto, K.; Amakura, Y.; Yoshimura, M.; Nakajima, M.; Furukawa, Y. 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. Molecules 2016, 21, 541.

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