Effects of Amanita muscaria extract on brain monoamines and potential applications in the treatment of neurodegenerative diseases

Introduction

In recent years, the increasing number of patients with neurodegenerative diseases has become a global concern, and the development of novel therapeutic agents is required.

Amanita muscaria is a poisonous mushroom containing central nervous system toxins. However, our previous studies have shown that it not only exhibits various bioactivities but also affects brain monoamines. Since brain monoamines are involved in the onset of many neurodegenerative diseases, we expect the potential application of A. muscaria as a novel therapeutic agent for these disorders. However, its active constituents, mechanisms of action, and effects of toxins remain unclear. Therefore, this study aimed to clarify the specific effects of A. muscaria on brain monoamines, identify its active constituents and evaluate its safety. We assessed the potential of A. muscaria for pharmaceutical application, and the results are reported herein.

Methods

Fruiting bodies of A. muscaria were collected in Abashiri City, Hokkaido, Japan. The brains of mice orally administered the hot-water extracts were homogenized, and the supernatant obtained after centrifugation was applied for high-performance liquid chromatography (HPLC) analysis to quantify the brain monoamines. The cell culture experiments using extracts from which toxic compounds had been removed by preparative HPLC were conducted using differentiated PC12 cells. Sugars and amino acids in the extracts were analyzed by an amino acid analyzer and HPLC. Statistical analyses were performed using one-way analysis of variance, followed by the Tukey–Kramer test.

Results and Discussion

Quantification of brain monoamines showed that dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) levels increased in a dose-dependent manner in mice administered the extract. Additionally, cell assays showed that monoamine-producing activity was retained even after removal of toxic components. A uniquely high concentration of the non-standard amino acid monoethanolamine (MEA) was identified in the extract. Based on this finding, MEA was added to PC12 cells, which resulted in increased monoamine production.

Since increased brain monoamines were observed following oral administration, the active constituents are likely to be capable of crossing the blood–brain barrier (BBB). A reduction in DA is implicated in the development of Parkinson’s disease. Therefore, these findings suggest that A. muscariahas potential as a therapeutic agent for neurodegenerative diseases. Additionally, bioactive components were observed apart from the toxic constituents. In particular, MEA is highly likely to be involved as an active ingredient. These results suggest that A. muscariacan be utilized as a medicinal agent irrespective of its toxic components, indicating its potential as a novel material for drug discovery.

Conclusions

This study revealed the potential application of A. muscaria as a novel therapeutic agent for neurodegenerative diseases. Furthermore, A. muscariawas shown to exhibit bioactivity irrespective of its toxic components, suggesting its potential utility as a novel material for drug development. Future work will focus on the detailed identification of the active constituents and further evaluation of efficacy using disease models. These findings provide a novel approach to drug discovery utilizing poisonous mushrooms and contribute to addressing the global challenge of treating neurodegenerative diseases.

References

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