The interaction of several herbal extracts with α-synuclein: Fibril formation and surface plasmon resonance analysis

PLoS One. 2019 Jun 11;14(6):e0217801. doi: 10.1371/journal.pone.0217801. eCollection 2019.

Abstract

Proteins from their native conformation convert into highly ordered fibrillar aggregation under particular conditions; that are described as amyloid fibrils. α-Synuclein (α-Syn) is a small natively unfolded protein that its fibrillation is the causative factor of Parkinson's disease. One important approach in the development of therapeutic agents is the use of small molecules (such as flavonoids) that could specifically and efficiently inhibit the aggregation process. In this study the effect of few herbal extract (Berberis, Quercus robur, Zizyphus vulgaris, Salix aegyptica) containing flavonoids were investigated on fibril formation of α-syn by using conventional methods such as ThT fluorescence, circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). The interaction of extracts were also analysed by surface plasmon resonance (SPR). Among extracts, Salix aegyptica revealed the highest inhibitory effect on fibril formation. As expected, Salix aegyptica extract also exhibited the highest affinity toward α-syn. Cell viability using MTT assay revealed that fibrils alone were more toxic than those containing the extract. Overall, we demonstrated that the affinity of compounds used in this study corresponds to their ability to arrest fibrillation and reduce cellular toxicity of α-syn fibrils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Cell Line, Tumor
  • Flavonoids / chemistry*
  • Humans
  • Plant Extracts / chemistry*
  • Plants, Medicinal / chemistry*
  • Protein Aggregates*
  • Surface Plasmon Resonance
  • alpha-Synuclein / chemistry*
  • alpha-Synuclein / metabolism

Substances

  • Amyloid
  • Flavonoids
  • Plant Extracts
  • Protein Aggregates
  • SNCA protein, human
  • alpha-Synuclein

Grants and funding

The present study was supported by grants from research council of Tarbiat Modares University and Iran National Science Foundation (INSF, project 93042561). The funders had no role in the study design, data collection and analysis, decision to publish and preparation of the manuscript.