Loading...

Identification of an aspidospermine derivative from borage extract as an anti-amyloid compound: A possible link between protein aggregation and antimalarial drugs

Kalhor, H. R ; Sharif University of Technology | 2017

1959 Viewed
  1. Type of Document: Article
  2. DOI: 10.1016/j.phytochem.2017.05.001
  3. Publisher: Elsevier Ltd , 2017
  4. Abstract:
  5. A number of human diseases, including Alzheimer's and Parkinson's have been linked to amyloid formation. To search for an anti-amyloidogenic product, alkaloid enriched extract from borage leaves was examined for anti-amyloidogenic activity using Hen Egg White Lysozyme (HEWL) as a model protein. After isolation of the plant extract using rHPLC, only one fraction indicated a significant bioactivity. TEM analysis confirmed a remarkable reduction of amyloid fibrils in the presence of the bioactive fraction. To identify the effective substance in the fraction, mass spectrometry, FTIR, and NMR were performed. Our analyses determined that the bioactive compound as 1-acetyl-19,21-epoxy-15,16-dimethoxyaspidospermidine-17-ol, a derivative of aspidospermine. To investigate the mechanism of the inhibition, ANS binding, intrinsic fluorescence, and amide I content were performed in the presence of the bioactive compound. All the results confirmed the role of the compound in assisting the proper folding of the protein. In addition, molecular docking indicated the aspidospermine derivative binds the amyloidogenic region of the protein. Our results show that the alkaloid extracted from borage leaves reduces protein aggregation mediating through structural elements of the protein, promoting the correct folding of lysozyme. Since a number of aspidospermine compounds have been shown to possess potent antimalarial activities, the action of compound identified in the present study suggests a possible link between protein aggregation and aspidospermine drugs. © 2017
  6. Keywords:
  7. Amyloid formation ; Aspidospermine ; Bioactive compound ; Borage officinalis ; Lysozyme ; Antimalarial agent ; Hen egg lysozyme ; Indole alkaloid ; Plant extract ; Quinoline derivative ; Antagonists and inhibitors ; Borago ; Chemistry ; Drug effects ; Isolation and purification ; Molecular docking ; Plant leaf ; Protein aggregation, pathological ; Amyloid ; Antimalarials ; Indole alkaloids ; Molecular docking simulation ; Muramidase ; Plant extracts ; Plant leaves ; Protein folding ; Quinolines
  8. Source: Phytochemistry ; Volume 140 , 2017 , Pages 134-140 ; 00319422 (ISSN)
  9. URL: https://www.sciencedirect.com/science/article/pii/S0031942217301930