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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2020

01-12-2020 | Parkinson's Disease | Research article

Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts

Authors: Mustafa T. Ardah, Simona S. Ghanem, Sara A. Abdulla, Guohua Lv, Mohamed M. Emara, Katerina E. Paleologou, Nishant N. Vaikath, Jia-Hong Lu, Min Li, Konstantinos Vekrellis, David Eliezer, Omar M. A. El-Agnaf

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

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Abstract

Background

Recent studies indicated that seeded fibril formation and toxicity of α-synuclein (α-syn) play a main role in the pathogenesis of certain diseases including Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy bodies. Therefore, examination of compounds that abolish the process of seeding is considered a key step towards therapy of several synucleinopathies.

Methods

Using biophysical, biochemical and cell-culture-based assays, assessment of eleven compounds, extracted from Chinese medicinal herbs, was performed in this study for their effect on α-syn fibril formation and toxicity caused by the seeding process.

Results

Salvianolic acid B and dihydromyricetin were the two compounds that strongly inhibited the fibril growth and neurotoxicity of α-syn. In an in-vitro cell model, these compounds decreased the insoluble phosphorylated α-syn and aggregation. Also, in primary neuronal cells, these compounds showed a reduction in α-syn aggregates. Both compounds inhibited the seeded fibril growth with dihydromyricetin having the ability to disaggregate preformed α-syn fibrils. In order to investigate the inhibitory mechanisms of these two compounds towards fibril formation, we demonstrated that salvianolic acid B binds predominantly to monomers, while dihydromyricetin binds to oligomeric species and to a lower extent to monomers. Remarkably, these two compounds stabilized the soluble non-toxic oligomers lacking β-sheet content after subjecting them to proteinase K digestion.

Conclusions

Eleven compounds were tested but only two showed inhibition of α-syn aggregation, seeded fibril formation and toxicity in vitro. These findings highlight an essential beginning for development of new molecules in the field of synucleinopathies treatment.
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Metadata
Title
Inhibition of alpha-synuclein seeded fibril formation and toxicity by herbal medicinal extracts
Authors
Mustafa T. Ardah
Simona S. Ghanem
Sara A. Abdulla
Guohua Lv
Mohamed M. Emara
Katerina E. Paleologou
Nishant N. Vaikath
Jia-Hong Lu
Min Li
Konstantinos Vekrellis
David Eliezer
Omar M. A. El-Agnaf
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-020-2849-1

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