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Kamikihito reduces β-amyloid25–35-induced axon damage via neurotrophic factors

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Abstract

The Japanese herbal medicine kamikihito (KKT) is widely used for insomnia, anorexia, anemia, and depression. Recently, the efficacy of KKT against Alzheimer's disease (AD) has been demonstrated in clinical and non-clinical studies. To address the mechanism underlying the effect of KKT on AD, we examined the effects of KKT in β-amyloid (Aβ)25–35-exposed primary cultured neurons. The effects of KKT on Aβ25–35-induced neurotoxicity were assessed by immunocytochemical assays and Sholl analysis of neurites, and the influence of KKT on neurotrophic factor (NF) gene expression was examined using RT-PCR analysis. As a result, Aβ25–35 exposure attenuated the arborization of neurites of single cultured hippocampal neurons, and KKT treatment for 3 days ameliorated the Aβ25–35-induced impairment of tau-positive axon outgrowth. This ameliorative effect of KKT was largely abolished by the Trk inhibitor K252a, and expression of NFs, nerve growth factor (Ngf), brain-derived neurotrophic factor (Bdnf), neurotrophin-3 (NT-3) was significantly increased by KKT. These results indicate that KKT ameliorates axonal atrophy via NFs signaling, providing a mechanistic basis for treatment of AD with KKT.

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Acknowledgements

The authors thank Takuya Matsuda, Naoyuki Okamura, Mayu Sakamoto, Erina Ishida, and Yuko Fukunaga for technical assistance. The authors are grateful to Tsumura & Co. (Tokyo, Japan) for generously supplying KKT and NYT. We thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by JSPS KAKENHI (K.K., 16K08315, 23K06204; T.W., 23K06249; K.I., 23K06203) and the Fukuoka University Program for Supporting the Research Activities of Female Researchers.

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Author notes

  1. Takumi Nagamatsu and Kaori Kubota contributed equally to this work.

Authors and Affiliations

  1. Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Takumi Nagamatsu, Kaori Kubota, Takuya Watanabe, Shutaro Katsurabayashi & Katsunori Iwasaki

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  1. Takumi Nagamatsu
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  2. Kaori Kubota
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  3. Takuya Watanabe
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  4. Shutaro Katsurabayashi
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  5. Katsunori Iwasaki
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Contributions

KK designed the study. TN and KK performed experiments and analyzed the data. TN, KK, and SK wrote the manuscript. TW, SK, and KI supervised the experiments. All authors read and approved the submitted manuscript.

Corresponding author

Correspondence to Kaori Kubota.

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Conflict of interest

Katsunori Iwasaki received a research grant (No. 20071, 20091) from Tsumura & Co. The other authors declare that they have no conflicts of interest.

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Nagamatsu, T., Kubota, K., Watanabe, T. et al. Kamikihito reduces β-amyloid25–35-induced axon damage via neurotrophic factors. J Nat Med 78, 246–254 (2024). https://doi.org/10.1007/s11418-023-01761-3

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