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

Phytochemistry
Hamid R Kalhor, Hossein Ashrafian

Abstract

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...Continue Reading

Citations

Dec 17, 2019·Current Pharmaceutical Design·Mahin RamezaniSeyed A Emami
Dec 6, 2020·International Journal of Biological Macromolecules·Hossein AshrafianRizwan Hasan Khan
Jun 8, 2021·International Journal of Biological Macromolecules·Hossein AshrafianRizwan Hassan Khan
Aug 5, 2017·The Journal of Physical Chemistry. B·Hamid R Kalhor, M Parsa Jabbari
Aug 25, 2018·Chemical Research in Toxicology·Hamid Reza Kalhor, Alireza Nazari Khodadadi
Nov 14, 2019·Journal of Chemical Information and Modeling·Hamid R Kalhor, Mohammadparsa Jabbary

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