Doliroside A from Dolichos falcata Klein suppressing amyloid β-protein 42 fibrillogenesis: An insight at molecular level

PLoS One. 2017 Oct 30;12(10):e0186590. doi: 10.1371/journal.pone.0186590. eCollection 2017.

Abstract

A bioactive chemical constituent, doliroside A, from Chinese traditional herbal medicine Dolichos falcata Klein was isolated, purified and identified by 60% ethanol extraction, thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) spectroscopy. Molecular interaction mechanism between doliroside and amyloid β42 protein was evaluated by thioflavin T fluorescence (ThT), circular dichroism (CD), atomic force microscope (AFM), and differential scanning calorimeter (DSC) from the aspects of kinetics, secondary structure, morphology, and thermodynamics, respectively. Results show that the purity of doliroside A is 99.9% by HPLC, and its chemical structure is identified by 1H- and 13C-NMR. Doliroside A is observed to be concentration-dependent inhibiting the fibrillation of Aβ42 with the IC50 value of 26.57 ± 1.6 μM. CD and DSC results imply that doliroside A can bind to the nuclei and oligomers of Aβ42 to form a stable complex and suppress Aβ42 fibrillation. AFM images show that doliroside A, after bound to the nuclei and oligomers, redirect Aβ42 into off-pathway, amorphous oligomers. These findings not only provide a full insight into the molecular interaction mechanisms between Aβ42 and doliroside A, but also facilitate the development of new native anti-AD drug of doliroside A compound.

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Chromatography, High Pressure Liquid
  • Circular Dichroism
  • Dolichos / chemistry*
  • Microscopy, Atomic Force
  • Molecular Structure
  • Proton Magnetic Resonance Spectroscopy
  • Saponins / chemistry
  • Saponins / pharmacology*
  • Thermodynamics

Substances

  • Amyloid beta-Peptides
  • Saponins
  • doliroside A

Grants and funding

This work was funded by the Ministry of Finance and the Ministry of Education of China. Additionally, this work was funded by the Beijing Municipal Natural Science Foundation (5142013 to YL) and the Fundamental Research Funds for the Central Universities, South-Central University for Nationalities of China (CZY10014 to QL). DSC equipments were provided by Prof. Zhaofeng Jiang and Dr. Ping Chang in Beijing Union University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.