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
- Authors
- Ko, Yong-Hyun; Kim, Sun Yeou; Lee, Seok-Yong; Jang, Choon-Gon
- Issue Date
- 5-May-2018
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- 6,7,4 ' -Trihydroxyisoflavone; Cognition; Brain-derived neurotrophic factor; cAMP response element binding; Alzheimer' s disease
- Citation
- EUROPEAN JOURNAL OF PHARMACOLOGY, v.826, pp.140 - 147
- Journal Title
- EUROPEAN JOURNAL OF PHARMACOLOGY
- Volume
- 826
- Start Page
- 140
- End Page
- 147
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3754
- DOI
- 10.1016/j.ejphar.2018.02.048
- ISSN
- 0014-2999
- Abstract
- 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.
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