2. Academic Validation
  3. 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

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

  • Int J Mol Sci. 2017 Oct 12;18(10):2133. doi: 10.3390/ijms18102133.
Atsushi Sawamoto 1,  Satoshi Okuyama 2,  Yoshiaki Amakura 3,  Morio Yoshimura 4,  Takashi Yamada 5,  Hidehiko Yokogoshi 6,  Mitsunari Nakajima 7,  Yoshiko Furukawa 8
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 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.
  • 5 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.
  • 6 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.
  • 7 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.
  • 8 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.
PMID: 29023414 DOI: 10.3390/ijms18102133
Abstract

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.

Keywords

3,5,6,7,8,3′,4′-heptamethoxyflavone; HMF; astrocyte; brain-derived neurotrophic factor; depression; neurogenesis; neuroplasticity.

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