The extract based on the Kampo formula daikenchuto (Da Jian Zhong Tang) induces Bdnf expression and has neurotrophic effects in cultured cortical neurons

Reductions in brain-derived neurotrophic factor (BDNF) expression levels have been reported in the brains of patients with neurological disorders such as Alzheimer’s disease. Therefore, upregulating BDNF and preventing its decline in the diseased brain could help ameliorate neurological dysfunctions...

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Bibliographic Details
Published in:Journal of natural medicines 2023-06, Vol.77 (3), p.584-595
Main Authors: Nakayama, Hironori, Ihara, Daisuke, Fukuchi, Mamoru, Toume, Kazufumi, Yuri, Chisato, Tsuda, Masaaki, Shibahara, Naotoshi, Tabuchi, Akiko
Format: Article
Language:English
Subjects:
Alzheimer's disease
Biomedical and Life Sciences
Biomedicine
Brain
Brain-derived neurotrophic factor
calcium
Calcium channels
Calcium channels (L-type)
Calcium channels (voltage-gated)
Calcium signalling
Complementary & Alternative Medicine
koi
Medicinal Chemistry
neurites
Neurodegenerative diseases
Neurological diseases
Neurological disorders
Original Paper
Panax
Pharmacology/Toxicology
Pharmacy
Plant Sciences
rhizomes
therapeutics
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Summary:Reductions in brain-derived neurotrophic factor (BDNF) expression levels have been reported in the brains of patients with neurological disorders such as Alzheimer’s disease. Therefore, upregulating BDNF and preventing its decline in the diseased brain could help ameliorate neurological dysfunctions. Accordingly, we sought to discover agents that increase Bdnf expression in neurons. Here, we screened a library of 42 Kampo extracts to identify those with the ability to induce Bdnf expression in cultured cortical neurons. Among the active extracts identified in the screen, we focused on the extract based on the Kampo formula daikenchuto. The extract of daikenchuto in the library used in this study was prepared using the mixture of Zingiberis Rhizoma Processum (ZIN), Zanthoxyli Piperiti Pericarpium (ZAN), and Ginseng Radix (GIN) without Koi. In this study, we defined DKT as the mixture of ZIN, ZAN, and GIN without Koi (DKT extract means the extract prepared from the mixture of ZIN, ZAN, and GIN without Koi). DKT extract significantly increased endogenous Bdnf expression by mediated, at least in part, via Ca 2+ signaling involving L-type voltage-dependent Ca 2+ channels in cultured cortical neurons. Furthermore, DKT extract significantly improved the survival of cultured cortical neurons and increased neurite complexity in immature neurons. Taken together, our findings suggest that DKT extract induces Bdnf expression and has a neurotrophic effect in neurons. Because BDNF inducers are expected to have therapeutic potential for neurological disorders, re-positioning of Kampo formulations such as daikenchuto may lead to clinical application in diseases associated with reduced BDNF in the brain. Graphical abstract
ISSN:1340-3443
1861-0293
DOI:10.1007/s11418-023-01703-z