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Hawaiian native herb Mamaki prevents dementia by ameliorating neuropathology and repairing neurons in four different mouse models of neurodegenerative diseases

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Abstract

Neurodegenerative diseases including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies are age-related disorders and the main cause of dementia. They are characterized by the cerebral accumulation of Aβ, tau, α-synuclein, and TDP-43. Because the accumulation begins decades before disease onset, treatment should be started in the preclinical stage. Such intervention would be long-lasting, and therefore, prophylactic agents should be safe, non-invasively taken by the patients, and inexpensive. In addition, the agents should be broadly effective against etiologic proteins and capable of repairing neurons damaged by toxic oligomers. These requirements are difficult to meet with single-ingredient pharmaceuticals but may be feasible by taking proper diets composed of multiple ingredients. As a source of such diets, we focused on the Hawaiian native herb Mamaki. From its dried leaves and fruits, we made three preparations: hot water extract of the leaves, non-extracted simple crush powder of the leaves, and simple crush powder of the fruits, and examined their effects on the cognitive function and neuropathologies in four different mouse models of neurodegenerative dementia. Hot water extract of the leaves attenuated neuropathologies, restored synaptophysin levels, suppressed microglial activation, and improved memory when orally administered for 1 month. Simply crushed leaf powder showed a higher efficacy, but simply crushed fruit powder displayed the strongest effects. Moreover, the fruit powder significantly enhanced the levels of brain-derived neurotrophic factor expression and neurogenesis, indicating its ability to repair neurons. These results suggest that crushed Mamaki leaves and fruits are promising sources of dementia-preventive diets.

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Data availability

Datasets used for analysis and materials are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Ayumi Yokota, Yu Masumoto, and Yuki Kinjo for technical assistance, and Peter Karagiannis for reading the manuscript.

Funding

This study was supported by funding from Cerebro Pharma Inc., Osaka, Japan.

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Authors and Affiliations

  1. Department of Translational Neuroscience, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Osaka, Abeno-ku, 545-8585, Japan

    Tomohiro Umeda, Keiko Shigemori, Rumi Uekado & Takami Tomiyama

  2. Cerebro Pharma Inc, 4-5-6-3F Minamikyuhojimachi, Osaka, Chuo-ku, 541-0058, Japan

    Tomohiro Umeda, Kazunori Matsuda & Takami Tomiyama

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  1. Tomohiro Umeda
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  2. Keiko Shigemori
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  4. Kazunori Matsuda
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Contributions

T.U. performed the experiments, analyzed the data, and prepared the figures. K.S. and R.U. carried out the experiments. K.M. prepared the materials. T.T. designed the study, performed the experiments, and wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takami Tomiyama.

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Ethics approval

All animal experiments were approved by the ethics committee of Osaka Metropolitan University and performed in accordance with the Guide for Animal Experimentation, Osaka Metropolitan University.

Competing interests

T.T. and K.M. are the founders of Cerebro Pharma Inc., and T.U. is a member of that company. The company funded this study and applied together with Osaka Metropolitan University for a patent on Mamaki. The other authors declare no competing interests.

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Umeda, T., Shigemori, K., Uekado, R. et al. Hawaiian native herb Mamaki prevents dementia by ameliorating neuropathology and repairing neurons in four different mouse models of neurodegenerative diseases. GeroScience 46, 1971–1987 (2024). https://doi.org/10.1007/s11357-023-00950-y

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